Alzheimer’s disease is mostly marked by dementia that includes memory problems, cognitive problems, executive dysfunction, and changes in attitude and behavior. Most people with this disease also have signs of a mental disorder. Careful attention and medicine can help with these signs for a short time, but there are no specific ways to stop or cure Alzheimer’s disease.

Dementia mostly affects older people, and the rates of occurrence and prevalence rise with age. This is more common in low- and middle-income countries and places. It is putting a lot of stress on families and societies in terms of money and illness. What does this mean for you if you have someone in your family with AD?

Based on studies of twins, AD is thought to be passed down 70% of the time. Clinically diagnosed AD has found more than 70 genomic loci in people with mostly European heritage. The discovery of these new genomic loci must be taken with a grain of salt.

Let’s look at what genetic inheritance can and cannot do and what may affect it. Even if you had a gene for a specific illness, even a serious mental illness, it might never be what we call “expressed” because there are a variety of things that must coalesce to make that happen.

A cell’s gene expression code is similar to a cookbook. Essential for all bodily functions, each gene is a blueprint for the production of a particular protein. The frequency with which your genes are activated or deactivated, or expressed, depends on a number of conditions.

At birth, you have a blueprint for your genes in the form of your DNA. But environmental factors, including your diet, level of physical activity, and smoking status, can affect gene expression. You name it; it can be impacted by factors including the medications you take.

Also, your gene expression might alter with age or specific medical issues. Although your DNA cannot be changed, there are certain things that can be altered, such as your lifestyle and the environment in which you are born. You can use this to keep yourself healthy and control certain medical issues.

Stress is one of the factors that has been indicated to potentially push these genes to become evident in behaviors, but what else could do it? There are too many variables regarding what might cause it to flare up, and the problem becomes knowing you have a gene for something specific and wondering if you will ever experience it in a behavior of some type.

It is possible that more than a third of cases of dementia could be avoided. Getting kids to go to school and exercise more, keeping up with friends and family, smoking less or quitting altogether, and taking care of hearing loss, depression, diabetes, high blood pressure, and obesity could all help avoid or delay dementia. There is also some early information about other risk factors that might be able to be changed.

What Does This Mean?

It is possible that further research based on these results may help diagnose and cure diseases in the future. Those who are concerned about the possibility of AD, or who have been found to have the genes, should consider the following:

1 Stay Informed: Learn about current research and developments in Alzheimer’s disease, the genetic basis of the disease, and how this can be managed through changes in lifestyle.

2. Talk about genetic risks. If your family has a history of Alzheimer’s disease, you should see your doctor about genetic testing to assess your risk.

3. Stick to the basics when it comes to keeping fit and avoiding illness — a healthy diet, regular exercise, keeping the mind active, and the control of chronic diseases such as diabetes and hypertension.

4. Consider participating in research. It is important that more people from different backgrounds become a part of the study to help advance research and develop more personalized treatments.

5. Keep talking to your doctor. Genetic study is interesting, but the best way to handle health issues is to prevent them from happening in the first place through the help of current treatments. If there is anything that you have concerns about or what to do next, you should report it to your healthcare provider.

How Do Interventions Work?

Lifestyle: Engaging in mental exercises on a regular basis, such as solving puzzles, reading, or picking up new skills, can help build cognitive reserve and potentially postpone the start of symptoms.

Sleep: The brain is able to eliminate toxic proteins and consolidate memories when you maintain a quality sleep routine of seven to eight hours per night.

Stress management: Reduced cortisol levels, which can eventually harm brain cells, are one benefit of stress management practices like mindfulness and meditation.

Smoking and alcohol: Promoting brain health through avoiding smoking and limiting alcohol use helps to maintain adequate blood flow and reduce inflammation. Smoking acts as a stress-reduction technique because nicotine is a natural substance reducing anxiety, but the downside is cancer.

Aerobic exercise promotes neuronal and synaptic growth by increasing blood flow to the brain, which carries oxygen and nutrients. By keeping insulin sensitivity high, resistance exercise protects against cognitive loss caused by diabetes and promotes overall brain health. Physical exercise improves clearance processes, which may lower beta-amyloid plaques, a characteristic of Alzheimer’s disease. Regular moderate exercise, even for just 150 minutes a week, improves cardiovascular health, decreases inflammation, and drastically reduces the risk of Alzheimer’s disease.

Socialization: The brain’s neural connections and plasticity are both supported by the cognitive stimulation that occurs during regular social contact, which is a key component of socialization. Potentially as a result of less stress and a stronger feeling of purpose, those with strong social networks have slower rates of cognitive deterioration. One of the most effective ways to stave off cognitive loss is to participate in group activities that mix socializing with mental or physical demands. Dementia risk factors include social isolation; in fact, research suggests that those who are lonely may have twice the chance of getting Alzheimer’s as those who have strong social connections.

Diet: The anti-inflammatory features of the Mediterranean and MIND diets have been associated with a substantially reduced risk of Alzheimer’s disease. These diets are rich in leafy greens, berries, nuts, fish, and olive oil. Free radicals damage brain cells and contribute to cognitive loss; foods rich in antioxidants can neutralize these radicals.

Overall, despite any genetic inheritance, we may have more power over our cognition than we have been led to believe in the past. Regularly attending to the above points can improve our mental and physical health, as shown by research, and lead to positive outcomes.

The post Alzheimer’s New Gene Discovery May Prove Decisive in Early Diagnosis or Not. What CAN You Do? appeared first on Medika Life.

First, a brief aside. I enjoy the work of sculptor Roland David Smith. This innovative American abstract expressionist painter and sculptor died in 1965 from a car crash at age 59.

Smith radically altered the terms of sculpture, a medium historically defined by casting, modeling, and carving. He was the first to use industrial welding as a sustained technique for large works.

I love his large abstract steel geometric sculptures. So here’s why my mind went to David Smith: I often most appreciate his sculptures when looking at them from different vantage points. They can be so radically different, depending on where you stand.

This perspective shift may be especially relevant when viewing Smith’s last works, the Cubi sculptures.

Today, most Cubi works are part of well-known museum collections, including the Museum of Modern Art in New York, the Tate Modern in London, and the Art Institute of Chicago.

Back to me and the perspective shift: Look from the side, and I have sufficient hair. From the front, still okay.

Now wander behind me as I sit in a chair, and voila: thinning hair on my crown. Consider me a Cubi (or perhaps Cubus?).

Hair Loss and Shedding

This morning, I read a piece in the New York Times entitled “Can Stress Cause Hair Loss?” I want to share some highlights from the article.

First, how many hairs do you think an average healthy individual sheds daily? According to the American Academy of Dermatology,

Healthy individuals shed approximately 50 to 100 strands of hair daily.

Are you losing more than that amount? You may have a condition with the unwieldy name of telogen effluvium or excessive hair shedding.

Stress

Can stress induce excessive hair shedding (telogen effluvium)? Yes, there are three hair loss types associated with high-stress levels. All have challenging names:

• Telogen effluvium (excessive hair loss). In telogen effluvium (TEL-o-jun uh-FLOO-vee-um), stress pushes numerous hair follicles into a resting phase. Within a few months, affected hairs might suddenly fall out when washing or combing your hair.
• Trichotillomania. Trichotillomania (trik-o-til-o-MAY-nee-uh) is an irresistible urge to pull hair from your scalp, eyebrows, or other areas. Some pull to cope with uncomfortable or negative feelings (such as tension, stress, boredom, frustration, or loneliness).
• Alopecia areata. Various factors are thought to cause alopecia areata (al-o-PEE-she-uh ar-e-A-tuh), including severe stress. With alopecia areata, the immune system attacks hair follicles, resulting in hair loss.

Hair Shedding Risk Factors

The American Academy of Dermatology Association offers that excessive hair shedding is common in people who have experienced any of these stressors:

• Experiencing lots of stress (caring for a loved one who is sick, going through a divorce, losing a job)
• Lost 20 pounds or more
• Given birth
• Had high fever
• Undergone an operation
• Recovering from an illness, especially if it includes a high fever
• Stopped taking birth-control pills

Excessive Hair Shedding — How Common Is It?

The incidence of excessive hair shedding is unclear; many individuals suffering from it never receive a diagnosis.

The condition is more common among women. Pregnancy is associated with excessive hair shedding. Fortunately, this hair loss tends to be temporary.

Writing in the New York Times, Dr. Angela Lamb, a dermatologist at Mount Sinai Hospital in New York City, offers this observation:

“People often develop telogen effluvium (excessive hair shedding) between six weeks and three months after a stressful event such as a major surgery, an illness (especially if it involved a fever), pregnancy or a death in the family — basically, anything that causes stress or shock to your system.

I was surprised to learn that this form of hair loss can occur after people recover from Covid-19. In a 2022 study, researchers surveyed almost 6,000 Brazilians who had recovered from Covid within the past three months. Nearly half of those who responded reported experiencing hair loss.

Hair Loss Differs from Shedding

Hair loss occurs when something stops hair from growing. For some, inherited genetics are the cause. Others have hair loss because of drugs or other treatments.

Certain hairstyles that pull on the hair can lead to hair loss. Sometimes, the immune system overreacts. In addition, some harsh hair products can be problematic.

Finally, some people have a compulsion to pull their hair.

Hair Shedding — Some Positive News

The good news? The American Academy of Dermatology Association offers this observation:

Most individuals see the excessive shedding stop after the body readjusts. Many see too much hair loss a few months after the stressful event; for example, some women see it peaking roughly four months post-delivery.

Within six to nine months, the hair regains its normal fullness.

On the other hand, if you don’t relieve yourself of the stress, the shedding can be chronic. Those under a lot of stress can see long-term excessive hair shedding.

If the stressor stays with you, hair shedding can be long-lived. People constantly under a lot of stress can have long-term excessive hair shedding.

Hair Loss — Get Input

Unfortunately, if you have hair loss, your hair won’t grow until the cause disappears. In my field of oncology, chemotherapy sometimes causes the loss of lots of hair. When the treatment stops, the hair usually regrows.

Talk to your healthcare provider if you are concerned that a particular medicine might be causing hair loss.

Other hair loss causes need treatment. Those with hereditary hair loss might find help with medicine or other interventions. Treatment can help many, but not all. A dermatologist can be an excellent resource for information.

If you notice sudden or patchy hair loss (or more than usual hair loss when washing or combing your hair), talk to a healthcare provider.

Sudden hair loss can be associated with an underlying medical condition (such as a thyroid problem) requiring management. Your doctor may also suggest treatment options for your hair loss.

Action Plan

Dr. Lamb suggests trying a daily multivitamin with vitamins D and B12 for those losing hair secondary to stress.

The former is involved in hair growth, while the latter might be deficient in some patients with telogen effluvium. Vitamins may be especially important around surgery.

On the other hand, Dr. Lamb does not recommend over-the-counter products high in biotin.

Such supplements have been shown to alter thyroid hormone test results, and the drugs sometimes cause acne flare-ups.

Many benefit from over-the-counter topical minoxidil treatment, such as Rogaine. Others get hair growth from prescribed medicine.

Minoxidil can accelerate shedding for several weeks or months before the shedding slows. Then, you may see re-growth. If shedding continues beyond three or four months, please check in with a valued healthcare professional.

Reduce Stress

Here are five ways that I reduce my stress levels:

1. I stay active. I love physical activity, whether walking or weightlifting.

2. I try to eat a healthy diet.

3. I have recently been better about regular meditation.

4. I love laughing.

5. I try to get at least seven hours of sleep (often coming up short by five to 15 minutes, alas).

Oh, my bald patch is the result of inherited genetics!

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Today we explore the clinical literature showing some studies reporting an association between low vitamin D levels and an increased risk of colorectal cancer, but others finding no such link.

Vitamin D and cancer — A randomized study

A 2018 clinical trial randomized participants to a control (marine omega-3 fatty acids, one gram daily) or vitamin D (cholecalciferol, 2000 IU daily).

The VITamin D and OmegA-3 TriaL (VITAL) clinical trial enrolled nearly 26,000 American men (50 and older) and women (55 and older) to examine the impact of vitamin D3 on several outcomes:

• Cancer prevention
• Cardiovascular disease risk (heart attack, stroke, and cardiovascular mortality).
• Secondary endpoints included site-specific cancers, cancer mortality, and additional cardiovascular events.

The results? With a median 5.3-year intervention, vitamin D supplementation did not reduce cancer or cardiovascular risk, the study’s two primary endpoints.

There appeared to be no significant differences in the secondary endpoints, either. The vitamin D3 intervention did not reduce the incidence of total cancer mortality or breast, prostate, or colorectal cancer. Finally, treatment effects did not differ by baseline vitamin D blood levels.

The researchers reported no excess risks of high calcium levels (hypercalcemia) or other side effects associated with vitamin D supplementation.

But are we sure that vitamin D3 supplementation does not reduce cancer risk? A 2019 meta-analysis analysis of the scientific literature concluded that:

Vitamin D3 did not reduce cancer incidence but did drop cancer mortality.

In addition, a secondary analysis of the VITAL clinical trial published in 2019 showed that while vitamin D supplementation did not lower cancer incidence, it appeared to be associated with a reduced incidence of advanced cancer.

My take

The VITAL clinical trial has tremendous strengths, including a large population with racial and geographic diversity. The daily vitamin D dosing seems reasonable, with follow-up blood collection in many participants showing blood levels in the target range.

The study has some significant limitations, however. For example, the researchers examined only a single dose of vitamin D3. Hopefully, future studies will look at another dose. Finally, the follow-up is not nearly long enough. For example, cancer can take decades from its birth before it is clinically observable.

We may also need to consider cancer risk by genotypes of vitamin D-associated genes.

Here are the US Preventative Services Task Force recommendations:

• Premenopausal women. The USPSTF recommends against daily supplementation with 400 IU or less of vitamin D and 1000 mg or less of calcium for the primary prevention of fractures in community-dwelling, postmenopausal women. Current evidence is insufficient to assess the balance of the benefits and harms of daily supplementation with doses greater than 400 IU of vitamin D and greater than 1000 mg of calcium for the primary prevention of fractures in community-dwelling, postmenopausal women.
• Men and premenopausal women. The USPSTF concludes that the current evidence is insufficient to assess the balance of the benefits and harms of vitamin D and calcium supplementation, alone or combined, for the primary prevention of fractures in men and premenopausal women.

Note this USPSTF observation: “These recommendations do not apply to persons with a history of osteoporotic fractures, increased risk for falls, or a diagnosis of osteoporosis or vitamin D deficiency.” Given we don’t routinely test for deficiency, how would I know if I am deficient?

Daily vitamin D3 supplementation for five years among initially healthy adults does not appear to lower cancer or major cardiovascular event risk. The evidence is insufficient to make supplement recommendations for community-dwelling individuals.

Thank you for joining me in this look at vitamin D and cancer risk. Today, I will not examine the impact of vitamin D (and vitamin K) on bone fracture risk.

The post Does Vitamin D Drop Cancer Risk? appeared first on Medika Life.

Just transplanting an animal’s organ into a human will not work. The person’s immune mechanisms will immediately reject the transplanted organ. So, what is to be done? The key is to genetically engineer the animal to produce organs that are less likely to be rejected. In the last 20 years, there’s been substantial progress on the research front to produce genetically modified pigs. Why pigs? Pig organs are about the same size as human organs but also share many physiologic similarities.

Recent technologies, including CRISPR, have allowed more possibilities to genetically engineer the pig’s genome. A few specific genes have been identified that are critical. Some were modified and some inactivated, called “knocked out.” It’s not just a matter of changing the pig’s genetics, but it’s also having a very specific anti-rejection drug combination. This includes the standard drugs used to prevent rejection of human organs and a specially designed monoclonal antibody against a part of the immune system called CD 40. This monoclonal antibody has been found to be essential and critical to the successful transplantation of a heart in the nonhuman primate model with animals maintained without rejection for upwards of 900 days.

In September 2021, a xenograft kidney from a genetically engineered pig was placed in a brain-dead patient still on life support. It was observed for 58 hours at the New York University Langone Hospital Center with the family’s permission to study for evidence of function and rejection. As a result, the surgical and research team, led by Dr. Robert Montgomery, himself a donor heart transplant recipient, were able to obtain critical information about the pig organ after transplantation. “Whole-body donation after death for the purpose of breakthrough studies represents a new pathway that allows an individual’s altruism to be realized after brain death declaration in circumstances in which their organs or tissues are not suitable for transplant.”

On Friday, January 7, Bartley Griffith, MD, Muhammad Mohiuddin, MD, and an extensive team of multi-specialties successfully implanted a genetically modified pig heart obtained from the Revivicor company. Revivicor created the genetically modified pig and hence the heart to the investigators’ specifications. This included modifying ten genes with three knocked out that lead to antibody development and one knocked out that controls the pig organs’ growth. The patient will also receive various anti-rejection drugs plus the monoclonal antibody aimed at CD40.

The patient, a 57-year-old man, was on life support and not eligible for a human donor organ. His projected lifespan was in days to weeks. He understood the risks of the procedure and that it was a first-time human experiment. But as he said before surgery, “It was either die or do this transplant. I want to live. I know it’s a shot in the dark, but it’s my last choice… I look forward to getting out of bed after I recover.”

The Food and Drug Administration (FDA,) having reviewed the research data, authorized the procedure “for compassionate use” on New Year’s Eve. As of Tuesday, January 12, the patient was doing well with no evidence of rejection. Only time will tell if he will make a full recovery and have his pig heart perform for many years.

Dr. Griffith is a cardiovascular surgeon with years of experience in transplanting human hearts and lungs. He has been working on xenotransplantation for over a decade. Dr. Mohiuddin joined with Dr. Griffith at the University of Maryland School of Medicine and Medical Center about five years ago to further pursue his research from the National Institutes of Health. He and colleagues developed the initial techniques to prevent rejection by gene modifications and anti-rejection drugs.

Together Griffith and Mohiuddin established the Xenotransplantation Center with Griffith as clinical director and Mohiuddin as scientific director. But, of course, there is a large team, not just the two of them. The Center investigators received a $15.7 million sponsored research grant to evaluate Revivicor genetically-modified pig hearts in further baboon studies. Last week’s surgery was the current culmination of those studies with a first in human heart xenotransplantation.

A new dawn has likely arrived for organ transplantation. But, of course, this was only the first patient. It remains to be seen how effective it will be in this man or how effective it will be in others treated with other genetically engineered pig organs like kidneys, pancreas, or lungs. But without question, it’s an exciting time with transplant-waiting individuals having a new potential on the horizon for returning to a reasonably normal life.

Stephen C Schimpff, MD, MACP, is a quasi-retired internist, professor of medicine, former CEO of the University of Maryland Medical Center, and author of Longevity Decoded — The 7 Keys to Healthy Aging and his co-authored book with Dr. Harry Oken BOOM — Boost Our Own Metabolism

The post A Pig Heart Was Transplanted Into a Human a Few Days Ago Is This The Future of Organ Transplantation? appeared first on Medika Life.

Date of Release:  Dec. 14, 2020

SAN FRANCISCO /PRNewswire/ — Over two million babies, children, and adults in the United States are living with congenital heart disease—a range of birth defects affecting the heart’s structure or function. Now, researchers at Gladstone Institutes and UC San Francisco (UCSF) have made inroads into understanding how a broad network of genes and proteins go awry in a subset of congenital heart diseases.

“We now have a better understanding of what genes are improperly deployed in some cases of congenital heart disease,” says Benoit Bruneau, PhD, director of the Gladstone Institute of Cardiovascular Disease and a senior author of the new study. “Eventually, this might help us get a handle on how to modulate genetic networks to prevent or treat the disease.”

Congenital heart disease encompasses a wide variety of heart defects, ranging from mild structural problems that cause no symptoms to severe malformations that disrupt or block the normal flow of blood through the heart. A handful of genetic mutations have been implicated in contributing to congenital heart disease; the first to be identified was in a gene known as TBX5. The TBX5 protein is a transcription factor—it controls the expression of dozens of others genes, giving it far-reaching effects.

Bruneau has spent the last 20 years studying the effect of TBX5 mutations on developing heart cells, mostly conducting research in mice. In the new study published in Developmental Cell, he and his colleagues turned instead to human cells, using novel approaches to follow what happens in individual cells when TBX5 is mutated.

“This is really the first time we’ve been able to study this genetic mutation in a human context,” says Bruneau, who is also a professor in the Department of Pediatrics at UCSF. “The mouse heart is a good proxy for the human heart, but it’s not exactly the same, so it’s important to be able to carry out these experiments in human cells.”

The scientists began with human induced pluripotent stem cells (iPS cells), which have been reprogrammed to an embryonic-like state, giving them—like embryonic stem cells—the ability to become nearly every cell type in the body.

Then, Bruneau’s group used CRISPR-Cas9 gene-editing technology to mutate TBX5 in the cells and began coaxing the iPS cells to become heart cells. As the cells became more like heart cells, the researchers used a method called single-cell RNA sequencing to track how the TBX5 mutation changed which genes were switched on and off in tens of thousands of individual cells.

The experiment revealed many genes that were expressed at higher or lower levels in cells with mutated TBX5. Importantly, not all cells responded to the TBX5 mutation in the same way; some had drastic changes in gene expression while other were less affected. This diversity, the researchers say, reflects the fact that the heart is composed of many different cell types.

“It makes sense that some are more affected than others, but this is the first experimental data in human cells to show that diversity,” says Bruneau.

Bruneau’s team then collaborated with computational researchers to analyze how the impacted genes and proteins were related to each other. The new data let them sketch out a complex and interconnected network of molecules that work together during heart development.

“We’ve not only provided a list of genes that are implicated in congenital heart disease, but we’ve offered context in terms of how those genes are connected,” says Irfan Kathiriya, MD, PhD, a pediatric cardiac anesthesiologist at UCSF Benioff Children’s Hospital, an associate professor in the Department of Anesthesia and Perioperative Care at UCSF, a visiting scientist at Gladstone, and the first author of the study.

Several genes fell into known pathways already associated with heart development or congenital heart disease. Some genes were among those directly regulated by TBX5’s function as a transcription factor, while others were affected in a less direct way, the study revealed. In addition, many of the altered genes were relevant to heart function in patients with congenital heart disease as they control the rhythm and relaxation of the heart, and defects in these genes are often found together with the structural defects.

The new paper doesn’t point toward any individual drug target that can reverse a congenital heart disease after birth, but a better understanding of the network involved in healthy heart formation, as well as congenital heart disease may lead to ways to prevent the defects, the researchers say. In the same way that folate taken by pregnant women is known to help prevent neural tube defects, there may be a compound that can help ensure that the network of genes and proteins related to congenital heart disease stays balanced during embryonic development.

“Our new data reveal that the genes are really all part of one network—complex but singular—which needs to stay balanced during heart development,” says Bruneau. “That means if we can figure out a balancing factor that keeps this network functioning, we might be able to help prevent congenital heart defects.”

About the Study

The paper “Modeling human TBX5 haploinsufficiency predicts regulatory networks for congenital heart disease,” was published by the journal Developmental Cell on December 14, 2020.

Other authors include Kavitha Rao, Patrick Devine, Andrew Blair, Swetansu Hota, Michael Lai, Bayardo Garay, Reuben Thomas, Piyush Goyal, Tatyana Sukonnik, Kevin Hu, Gunes Akgun, and Laure Bernard of Gladstone; Giovanni Iacono and Holger Heyn of Barcelona Institute of Science and Technology; Henry Gong, Matthew Speir, Maximilian Haeussler, and Joshua Stuart of the University of California, Santa Cruz; Lauren Wasson, Christine Seidman, and J. G. Seidman of Harvard Medical School; and Brynn Akerberg, Fei Gu, Kai Li, and William Pu of Boston Children’s Hospital.

The work was supported by grants from the National Institutes of Health (UM1HL098179, UM1HL098166, R01HL114948, USCF CVRI 2T32HL007731-27), the California Institute for Regenerative Medicine (RB4-05901), the Office of the Assistant Secretary of Defense for Health Affairs (W81XWH-17-1-0191), the Foundation for Anesthesia Education and Research, the Society for Pediatric Anesthesia, the Hellman Family Fund, the UCSF REAC Grant, and the UCSF Department of Anesthesia and Perioperative Care.

About Gladstone Institutes

To ensure our work does the greatest good, Gladstone Institutes focuses on conditions with profound medical, economic, and social impact—unsolved diseases. Gladstone is an independent, nonprofit life science research organization that uses visionary science and technology to overcome disease. It has an academic affiliation with UC San Francisco.

Media Contact: Julie Langelier | Assistant Director, Communications | julie.langelier@gladstone.org | 415.734.5000
1650 Owens Street, San Francisco, CA 94158 | gladstone.org | @GladstoneInst

SOURCE Gladstone Institutes

Related Links

https://gladstone.org

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Mutations in these two genes don’t just increase your risk of breast cancer. Mutations on both increase the risk of ovarian cancer and pancreatic cancer. A BRCA1 mutation can increase the risk of cervical, uterine, and colon cancer, while mutations on BRCA2 can increase the likelihood of stomach, gallbladder, and bile duct cancer, and melanoma.

There a really good reason for this. These genes are known as “tumor suppressors,” and when they function normally, they help to maintain cell growth at the appropriate rate. When harmful mutations are present, cells have the potential for unchecked growth, increasing your risk of breast cancer.

Do I have the BRCA 1 and 2 Genes?

Yes, everyone does as they are passed on to you by both parents, so everyone has two copies of each gene. If a harmful mutation of one of these genes is inherited from a parent, every cell in the body will possess one mutated copy of the gene and one normal copy. 

As long as the other copy continues to function normally, breast cancer will not develop, which is why not every woman with a harmful mutation gets cancer. Her risk factor is much higher, but it’s certainly not a guarantee of breast cancer. However, if the other copy of the gene is altered or mutated later in her life, cancer can occur.

The part of the body where that second mutation occurs, such as the breast or the ovary determines where the cancer will develop. Science still doesn’t know exactly what causes these secondary mutations, but it may be due to other biological or environmental risk factors.

Since the harmful mutations are inherited from either the mother or the father, family history on either side is the best indication of whether the mutation is present. Doctors will look for specific “warning signs”, including:

• Two first-degree relatives (mom, daughter, sister) with breast cancer, or if one was diagnosed at 50 or younger
• Three or more first- or second-degree relatives (including grandmother or aunt), regardless of age
• Any first-degree relative with cancer diagnosed in both breasts
• Any first or second degree relative diagnosed with both breast and ovarian cancer
• Breast cancer in a male relative

Certain ethnic groups are also at a higher risk of having these mutations, including those with Ashkenazi Jewish backgrounds, and some Scandinavian, Dutch, and Icelandic peoples. In particular, Ashkenazi Jewish people (a certain group of Central European descent) have as high as a 1 in 40 chance of possessing a harmful mutation of BRCA1 or BRCA2.

How much does my risk of cancer increase if I do have the mutation?

Recent breast cancer statistics suggest that 1 in 8 women will be diagnosed with breast cancer in their lifetime. Approximately 60 percent of women who have inherited these harmful gene mutations will develop breast cancer. That’s 3-in-5 so their is a marked increase in risk. It’s very important though to remember the following;

• Not all breast cancer is due to these genetic mutations. Not every woman with a harmful mutation gets cancer. Her risk factor is much higher, but it’s certainly not a guarantee of breast cancer.
• Scientists’ best estimates suggest that only 5 to 10 percent of breast cancers are due to the mutations of BRCA1 and BRCA2.
• Not all women with the mutation will develop breast cancer, but, more than half of them will, and many at an earlier age than the average diagnosis.

Testing For BRCA1 and 2 Mutations

Testing for these mutations is available, but can be quite expensive. Pricing usually starts at several hundred dollars and can cost as much as several thousand. Thanks to the Affordable Care Act, the tests are now guaranteed to be covered by insurance if an individual meets certain criteria in terms of family history, but those criteria are very specific and only about 2 percent of the general population will meet them.

The tests are simple blood tests that are conducted in a doctor’s office, clinic, hospital, or laboratory, and then sent to a testing company. It can take several weeks to receive the results, and genetic counseling both before and after the test is highly recommended. Learning about the presence of a mutation on the genes can be difficult, so it’s important to fully understand the implications and possible responses.

Again, a positive test result doesn’t guarantee that you will develop breast cancer, but it does mean your risk factor is approximately 3-in-5 instead of 1-in-8, so some sort of proactive response is recommended.

I’ve tested positive, what are my options?

Women who do test positive have a few options. Being proactive is especially important to ensure early detection. Increased monthly breast self-exams, clinical breast exams, and mammograms, all beginning at an earlier age are all recommended to ensure early detection.

Prophylactic surgery, which removes as much of the at-risk breast tissue as possible to reduce the chance of cancer developing in the breast can also be discussed by the doctor and patient. It isn’t a guarantee that breast cancer will never appear, but it definitely reduces the risk. Preventative drug treatments are also available, but more study is needed to determine how useful these might be..

The post BRCA1 and 2: The Breast Cancer Genes appeared first on Medika Life.

So what exactly do these tests offer? What can you test for and how reliable are the results? Are there any pitfalls and warning signs that suggest you should be wary of a service and what are the risks of your genetic data being shared? Lets start with a definition of DTC Genetic testing and then first address what these tests cannot do.

What is DTC Genetic Testing?

Most of the time, genetic testing is done through healthcare providers such as physicians, nurse practitioners, and genetic counselors. Healthcare providers determine which test is needed, order the test from a laboratory, collect and send the DNA sample, interpret the test results, and share the results with the patient.

Direct-to-consumer genetic testing is different: these genetic tests are marketed directly to customers via television, print media, or the Internet, and the tests can be bought online or in stores. Customers send the company a DNA sample and receive their results directly from a secure website or in a written report.

Direct-to-consumer genetic testing provides people access to certain of their genetic information without necessarily involving a healthcare provider or health insurance company in the process.

Dozens of companies currently offer these tests for a variety of purposes. The most popular tests use genetic variations to make predictions about health, provide information about common traits, and offer clues about a person’s ancestry. The number of companies is growing, along with the range of health conditions and traits covered by these tests.

Because there is currently little regulation of direct-to-consumer genetic testing services, it is important to assess the quality of available services before pursuing any testing.

Will a DTC Genetic test tell me if I’m likely to get cancer?

While a direct-to-consumer genetic test can estimate your risk, it cannot tell you for certain whether you will or will not develop certain forms of cancer. Many other factors, including gender, age, diet and exercise, ethnic background, a history of previous cancer, hormonal and reproductive factors, and family history also contribute to a person’s overall cancer risk.

The U.S. Food and Drug Administration (FDA) has allowed at least one direct-to-consumer genetic testing company, 23andMe, to offer a test for cancer risk. The test looks for three specific variations in two genes: BRCA1 and BRCA2. These variations are associated with an increased risk of breast cancer, ovarian cancer, and potentially other forms of cancer in people of Ashkenazi (eastern European) Jewish ancestry.

Researchers estimate that 5 to 10 percent of all cancers run in families. Some of these cancers are associated with inherited mutations in particular genes, such as BRCA1 or BRCA2. More than 1,000 variations in each of these genes have been associated with an increased risk of cancer. However, the FDA-approved direct-to-consumer genetic test analyzes only three of these variations. The variations included in the test are much more common in people of Ashkenazi Jewish background than in people of other ethnicities, so if you are not of Ashkenazi Jewish heritage, the results may not be useful to you.

Because the variants included in the test are uncommon, most people will have a negative result. A negative result does not mean that you will never get cancer. Similarly, a positive result (one that indicates a cancer-related genetic variation) does not mean that you will definitely develop cancer.

Can a DTC genetic test tell if I will develop Alzheimer disease?

While a direct-to-consumer genetic test can estimate your risk, it cannot tell you for certain whether you will or will not develop Alzheimer disease. Variations in multiple genes, together with lifestyle factors such as diet and exercise, all play a role in determining a person’s risk.

The U.S. Food and Drug Administration (FDA) has allowed at least one direct-to-consumer genetic testing company, 23andMe, to offer a test for Alzheimer disease risk. The test analyzes a gene called APOE. Certain variations in this gene are associated with the likelihood of developing late-onset Alzheimer disease (the most common form of the condition, which begins after age 65).

Specifically, the test allows you to find out how many copies (zero, one, or two) you have of a version of the gene called the e4 allele. People who have zero copies of the e4 allele have the same risk of late-onset Alzheimer disease as the general population. The risk increases with the number of copies of the e4 allele, so people with one copy have an increased chance of developing the disease, and people with two copies have an even greater risk.

However, many people who have one or two copies of the e4 allele never develop Alzheimer disease, and many people with no copies of this allele ultimately get the disease.

Variations in the APOE gene are among many factors that influence a person’s overall risk of developing Alzheimer disease. Variations in many other genes, which are not reported in the FDA-approved direct-to-consumer genetic test, also contribute to disease risk. Additionally, there are risk factors for Alzheimer disease that have yet to be discovered.

The APOE e4 allele represents only one piece of your overall Alzheimer disease risk. It is not definitive, but one of many possible indicators.

Can the results of DTC genetic testing affect my ability to get insurance?

A federal law passed in 2008 called the Genetic Information Nondiscrimination Act (GINA) made it illegal for health insurance providers in the United States to use genetic information in decisions about a person’s health insurance eligibility or coverage. That however does not prevent Insurance companies from requesting this data as part of your medical history and GINA does not apply when an employer has fewer than 15 employees.

GINA does not apply to other forms of insurance, such as disability insurance, long-term care insurance, or life insurance. Companies that offer these policies have the right to request medical information, including the results of any genetic testing, when making decisions about coverage and rates. You should weigh the possible benefits and risks, including potential impacts on insurance eligibility and coverage, before you start the testing process.

What DTC Genetic tests are available?

With so many companies offering direct-to-consumer genetic testing, it can be challenging to determine which tests will be most informative and helpful to you. When considering testing, think about what you hope to get out of the test. Some are very specific (paternity tests), while other services provide a broad range of health, ancestry, and lifestyle information.

Disease risk and health

The results of these tests estimate your genetic risk of developing several common diseases, such as celiac disease, Parkinson disease, and Alzheimer disease. Some companies also include a person’s carrier status for less common conditions, including cystic fibrosis and sickle cell disease. A carrier is someone who has one copy of a gene mutation that, when present in two copies, causes a genetic disorder.

The tests may also look for genetic variations related to other health-related traits, such as weight and metabolism (how a person’s body converts the nutrients from food into energy).

Ancestry or genealogy

The results of these tests provide clues about where a person’s ancestors might have come from, their ethnicity, and genetic connections between families.

Kinship

The results of these tests can indicate whether tested individuals are biologically related to one another. For example, kinship testing can establish whether one person is the biological father of another (paternity testing). The results of direct-to-consumer kinship tests, including paternity tests, are usually not admissible in a court of law.

Lifestyle

The results of these tests claim to provide information about lifestyle factors, such as nutrition, fitness, weight loss, skincare, sleep, and even your wine preferences, based on variations in your DNA. Many of the companies that offer this kind of testing also sell services, products, or programs that they customize on the basis of your test results.

Before choosing a test, find out what kinds of health, ancestry, or other information will be reported to you. Think about whether there is any information you would rather not know. In some cases, you can decline to find out specific information if you tell the company before it delivers your results.

A more detailed look at Genetic Ancestry Testing

Genetic ancestry testing, or genetic genealogy, is a way for people interested in family history (genealogy) to go beyond what they can learn from relatives or from historical documentation. Examination of DNA variations can provide clues about where a person’s ancestors might have come from and about relationships between families. Certain patterns of genetic variation are often shared among people of particular backgrounds. The more closely related two individuals, families, or populations are, the more patterns of variation they typically share.

Three types of genetic ancestry testing are commonly used for genealogy:

Y chromosome testing

Variations in the Y chromosome, passed exclusively from father to son, can be used to explore ancestry in the direct male line. Y chromosome testing can only be done on males, because females do not have a Y chromosome. However, women interested in this type of genetic testing sometimes recruit a male relative to have the test done. Because the Y chromosome is passed on in the same pattern as are family names in many cultures, Y chromosome testing is often used to investigate questions such as whether two families with the same surname are related.

Mitochondrial DNA testing

This type of testing identifies genetic variations in mitochondrial DNA. Although most DNA is packaged in chromosomes within the cell nucleus, cell structures called mitochondria also have a small amount of their own DNA (known as mitochondrial DNA). Both males and females have mitochondrial DNA, which is passed on from their mothers, so this type of testing can be used by either sex. It provides information about the direct female ancestral line. Mitochondrial DNA testing can be useful for genealogy because it preserves information about female ancestors that may be lost from the historical record because of the way surnames are often passed down.

Single nucleotide polymorphism testing

These tests evaluate large numbers of variations (single nucleotide polymorphisms or SNPs) across a person’s entire genome. The results are compared with those of others who have taken the tests to provide an estimate of a person’s ethnic background. For example, the pattern of SNPs might indicate that a person’s ancestry is approximately 50 percent African, 25 percent European, 20 percent Asian, and 5 percent unknown.

Genealogists use this type of test because Y chromosome and mitochondrial DNA test results, which represent only single ancestral lines, do not capture the overall ethnic background of an individual.

Genetic ancestry testing has a number of limitations. Test providers compare individuals’ test results to different databases of previous tests, so ethnicity estimates may not be consistent from one provider to another. Also, because most human populations have migrated many times throughout their history and mixed with nearby groups, ethnicity estimates based on genetic testing may differ from an individual’s expectations.

In ethnic groups with a smaller range of genetic variation due to the group’s size and history, most members share many SNPs, and it may be difficult to distinguish people who have a relatively recent common ancestor, such as fourth cousins, from the group as a whole.

Genetic ancestry testing is offered by several companies and organizations. Most companies provide online forums and other services to allow people who have been tested to share and discuss their results with others, which may allow them to discover previously unknown relationships.

On a larger scale, combined genetic ancestry test results from many people can be used by scientists to explore the history of populations as they arose, migrated, and mixed with other groups.

Selecting a company for your DTC Genetic Test

If you are interested in direct-to-consumer genetic testing, do some research into the companies that offer these services. Questions that can help you assess the quality and credibility of a testing company include:

• Does the company’s website appear professional? Does the company provide adequate information about the services it offers, including sample reports, pricing, and methodology?
• Does the company have experienced genetics professionals, such as medical geneticists and genetic counselors, on its staff? Does the company offer consultation with a genetics professional if you have questions about your test results?
• Does the company explain which genetic variations it is testing for? Does it include the scientific evidence linking those variations with a particular disease or trait? Are the limitations of the test and the interpretation of results made clear?
• What kind of laboratory does the genetic testing, and is the laboratory inside or outside the United States? Is the laboratory certified or accredited? For example, does the laboratory meet U.S. federal regulatory standards called the Clinical Laboratory Improvement Amendments (CLIA)? Is the test approved by the U.S. Food and Drug Administration (FDA)?
• Does the company indicate how it will protect your privacy and keep your genetic data safe? Does that information include both current privacy practices and what may happen to your genetic data in the future?
• Does the company indicate who will have access to your data and how it may be shared? Does it share or sell their customers’ genetic data for research or other purposes? For some companies, much of their profit comes from selling large amounts of participant data for research and drug development, not from selling individual test kits.

Be sure to read and understand the “fine print” on the company’s website before purchasing a test. This detailed information, which is often called the “terms of use” or “terms of service,” is a legally binding agreement between you and the company providing the testing.

It spells out what is included and excluded in the service and details your rights and the company’s responsibilities. If you still have questions, contact the company to get more information before you make a decision about testing.

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• FBN
• FBN1_HUMAN
• fibrillin 1 (Marfan syndrome)
• MFS1
• SGS

The FBN1 gene provides instructions for making a large protein called fibrillin-1. This protein is transported out of cells into the extracellular matrix, which is an intricate lattice of proteins and other molecules that forms in the spaces between cells. In this matrix, molecules of fibrillin-1 attach (bind) to each other and to other proteins to form threadlike filaments called microfibrils.

Microfibrils form elastic fibers, which enable the skin, ligaments, and blood vessels to stretch. Microfibrils also provide support to more rigid tissues such as bones and the tissues that support the nerves, muscles, and lenses of the eyes. Microfibrils store a protein called transforming growth factor beta (TGF-β), a critical growth factor.

TGF-β affects development by helping to control the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (motility), and the self-destruction of cells (apoptosis). Microfibrils help regulate the availability of TGF-β, which is turned off (inactivated) when stored in microfibrils and turned on (activated) when released.

Health Conditions related to genetic changes of FBN1

Acromicric Dysplasia

At least nine FBN1 gene mutations have been identified in people with acromicric dysplasia. This condition is characterized by severely short stature, short limbs, stiff joints, and distinctive facial features.

FBN1 gene mutations that cause acromicric dysplasia are located in an area of the gene called exons 41 and 42, and change single protein building blocks (amino acids) in a region of the fibrillin-1 protein called TGF-β binding-protein-like domain 5. The mutations result in a reduction and disorganization of the microfibrils. Without enough normal microfibrils to store TGF-β, the growth factor is abnormally active. These effects likely contribute to the physical abnormalities that occur in acromicric dysplasia, but the mechanisms are unclear.

It is unknown why the FBN1 gene mutations that cause acromicric dysplasia lead to short stature, while certain other FBN1 gene mutations that also increase TGF-β activity cause a disorder called Marfan syndrome (see below), which is characterized by tall stature.

Isolated Ectopia Lentis

More than 30 mutations in the FBN1 gene have been found to cause isolated ectopia lentis. In this condition, the lens in one or both eyes is off-center (displaced), which leads to vision problems. Most of the FBN1 gene mutations that cause this condition change single amino acids in the fibrillin-1 protein. As a result, the production of normal fibrillin-1 protein is reduced, leading to a decrease in microfibril formation or the formation of impaired microfibrils.

Without enough functional microfibrils to anchor the lens in its central position at the front of the eye, the lens becomes displaced, resulting in isolated ectopia lentis and related vision problems. Ectopia lentis is classified as isolated when it occurs alone, without signs and symptoms affecting other body systems.

However, some people initially diagnosed with isolated ectopia lentis caused by FBN1 gene mutations later develop additional features typical of a condition called Marfan syndrome (described below), such as abnormalities of the large blood vessel that distributes blood from the heart to the rest of the body (the aorta). In these cases, the diagnosis often changes from isolated ectopia lentis to Marfan syndrome.

Marfan Syndrome

Researchers have identified more than 1,300 FBN1 gene mutations that cause Marfan syndrome, a disorder that affects the connective tissue supporting the body’s joints and organs. Abnormalities in the connective tissue lead to heart and eye problems in people with this disorder. In addition, affected individuals are usually tall and slender with elongated fingers and toes and other skeletal abnormalities.

Most of the mutations that cause Marfan syndrome change a single amino acid in the fibrillin-1 protein. The remaining FBN1 gene mutations result in an abnormal fibrillin-1 protein that cannot function properly. FBN1 gene mutations that cause Marfan syndrome reduce the amount of fibrillin-1 produced by the cell, alter the structure or stability of fibrillin-1, or impair the transport of fibrillin-1 out of the cell.

These mutations lead to a severe reduction in the amount of fibrillin-1 available to form microfibrils. Without enough microfibrils, excess TGF-β growth factors are activated and elasticity in many tissues is decreased, leading to overgrowth and instability of tissues and the signs and symptoms of Marfan syndrome.

Weill-Marchesani syndrome

Mutations in the FBN1 gene have also been identified in Weill-Marchesani syndrome. One of the identified mutations deletes part of the gene, leading to the production of an unstable version of the fibrillin-1 protein. The unstable protein likely interferes with the assembly of microfibrils. Abnormal microfibrils weaken connective tissue, which causes the eye, heart, and skeletal abnormalities associated with Weill-Marchesani syndrome.

Other Disorders

Mutations in the FBN1 gene can cause a condition called stiff skin syndrome. This condition is characterized by very hard, thick skin covering most of the body. The abnormal skin limits movement and can lead to joint deformities called contractures that restrict the movement of certain joints. The signs and symptoms of stiff skin syndrome usually become apparent in infancy to mid-childhood.

Mutations in the FBN1 gene can cause another condition called MASS syndrome. This condition involves abnormalities in several parts of the body, including the mitral valve (one of the valves that controls blood flow through the heart), the aorta (a large blood vessel that distributes blood from the heart to the rest of the body), the skeleton, and the skin.

It is unknown why different mutations in the FBN1 gene cause such a variety of disorders.

Chromosomal Location

Cytogenetic Location: 15q21.1, which is the long (q) arm of chromosome 15 at position 21.1

Molecular Location: base pairs 48,408,313 to 48,645,709 on chromosome 15 (Homo sapiens Updated Annotation Release 109.20200522, GRCh38.p13) (NCBI)

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Because connective tissue is found throughout the body, Marfan syndrome can affect many systems, often causing abnormalities in the heart, blood vessels, eyes, bones, and joints. The two primary features of Marfan syndrome are vision problems caused by a dislocated lens (ectopia lentis) in one or both eyes and defects in the large blood vessel that distributes blood from the heart to the rest of the body (the aorta).

The aorta can weaken and stretch, which may lead to a bulge in the blood vessel wall (an aneurysm). Stretching of the aorta may cause the aortic valve to leak, which can lead to a sudden tearing of the layers in the aorta wall (aortic dissection). Aortic aneurysm and dissection can be life threatening.

Many people with Marfan syndrome have additional heart problems including a leak in the valve that connects two of the four chambers of the heart (mitral valve prolapse) or the valve that regulates blood flow from the heart into the aorta (aortic valve regurgitation). Leaks in these valves can cause shortness of breath, fatigue, and an irregular heartbeat felt as skipped or extra beats (palpitations).

Individuals with Marfan syndrome are usually tall and slender, have elongated fingers and toes (arachnodactyly), loose joints, and have an arm span that exceeds their body height. Other common features include a long and narrow face, crowded teeth, an abnormal curvature of the spine (scoliosis or kyphosis), stretch marks (striae) not related to weight gain or loss, and either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum).

Some individuals develop an abnormal accumulation of air in the chest cavity that can result in the collapse of a lung (spontaneous pneumothorax). A membrane called the dura, which surrounds the brain and spinal cord, can be abnormally enlarged (dural ectasia) in people with Marfan syndrome. Dural ectasia can cause pain in the back, abdomen, legs, or head.

Most individuals with Marfan syndrome have some degree of nearsightedness (myopia). Clouding of the lens (cataract) may occur in mid-adulthood, and increased pressure within the eye (glaucoma) occurs more frequently in people with Marfan syndrome than in those without the condition.

The features of Marfan syndrome can become apparent anytime between infancy and adulthood. Depending on the onset and severity of signs and symptoms, Marfan syndrome can be fatal early in life; however, with proper treatment, many affected individuals have normal lifespans.

Causes of Marfan

The prevalence of Marfan Syndromw among the general public is approximately 1 in 5000 people.

Mutations in the FBN1 gene cause Marfan syndrome. The FBN1 gene provides instructions for making a protein called fibrillin-1. Fibrillin-1 attaches (binds) to other fibrillin-1 proteins and other molecules to form threadlike filaments called microfibrils. Microfibrils become part of the fibers that provide strength and flexibility to connective tissue. Additionally, microfibrils bind to molecules called growth factors and release them at various times to control the growth and repair of tissues and organs throughout the body.

A mutation in the FBN1 gene can reduce the amount of functional fibrillin-1 that is available to form microfibrils, which leads to decreased microfibril formation. As a result, microfibrils cannot bind to growth factors, so excess growth factors are available and elasticity in many tissues is decreased, leading to overgrowth and instability of tissues in Marfan syndrome.

Inheritance Pattern

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

At least 25 percent of Marfan syndrome cases result from a new mutation in the FBN1 gene. These cases occur in people with no history of the disorder in their family.

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Alpha-1 antitrypsin prevents the digestive enzyme trypsin from breaking down proteins until trypsin reaches the intestines. Alpha-1 antitrypsin also inhibits other enzymes, including a powerful enzyme called neutrophil elastase that is released from white blood cells to fight infection.

Alpha-1 antitrypsin protects the lungs from neutrophil elastase, which can damage lung tissue if not properly controlled. Alpha-1 antitrypsin is produced in the liver and then transported to the lungs via the blood.

Alpha-1 antitrypsin Deficiency

More than 120 mutations in the SERPINA1 gene have been identified. Some of these mutations do not affect the production of alpha-1 antitrypsin, while others cause a shortage (deficiency) of the protein. Without enough functional alpha-1 antitrypsin, neutrophil elastase destroys the small air sacs in the lungs (alveoli) and causes lung disease. Excessive damage to the alveoli leads to emphysema, an irreversible lung disease that causes extreme shortness of breath.

Many SERPINA1 gene mutations change single protein building blocks (amino acids) in alpha-1 antitrypsin, which alters the protein’s structure. The most common mutation that causes alpha-1 antitrypsin deficiency replaces the amino acid glutamic acid with the amino acid lysine at protein position 342 (written as Glu342Lys or E342K). This mutation results in a version of the SERPINA1 gene called the Z allele that produces very little alpha-1 antitrypsin.

Abnormal alpha-1 antitrypsin proteins may bind together to form a large molecule, or polymer, that cannot leave the liver. The accumulation of these polymers results in liver damage. In addition, lung tissue is destroyed because not enough alpha-1 antitrypsin is available to protect against neutrophil elastase. Polymers of alpha-1 antitrypsin may also contribute to excessive inflammation, which may explain some of the other features of alpha-1 antitrypsin deficiency, such as a skin condition called panniculitis.

Other SERPINA1 gene mutations lead to the production of an abnormally small form of alpha-1 antitrypsin that is quickly broken down in the liver. As a result, little or no alpha-1 antitrypsin is available in the lungs. While the liver remains healthy in individuals with these mutations, the lungs are left unprotected from neutrophil elastase.

Chromosomal Location

Cytogenetic Location: 14q32.13, which is the long (q) arm of chromosome 14 at position 32.13

Molecular Location: base pairs 94,376,747 to 94,390,654 on chromosome 14 (Homo sapiens Updated Annotation Release 109.20200522, GRCh38.p13) (NCBI)

This gene is also referred to as

• A1A
• A1AT
• A1AT_HUMAN
• AAT
• alpha-1 antiproteinase
• alpha-1 antitrypsin
• alpha-1 proteinase inhibitor
• alpha1AT
• PI
• PI1
• protease inhibitor 1 (anti-elastase)
• serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1
• serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1

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