Talk

Marfan syndrome has been in the news a bit recently (”Old Drug Offers New Hope for Marfan Syndrome“). Perhaps not coincidentally over at MedHelp’s Genetics Forum, our senior Genetic Counselor Lisa Kessler has received a few questions about Marfan syndrome.

Marfan syndrome is an inherited disorder that affects the connective tissues, which hold the body together and are involved in growth. Marfan syndrome can also affect the heart and blood vessels, bones, cartilege and ligaments, eyes, lungs, and skin. According to Janis Cortese, it’s also “a big pain in the ass.”

Named after Antoine Marfan, the French pediatrician who first described the condition in 1896, Marfan syndrome affects an estimated 1 in 5000 people. It is inherited in a dominant manner: if one parent has Marfan syndrome, each child has a 1 in 2 (or 50%) chance of inheriting it, too.

With today’s early diagnosis and better medical and surgical treatments, people with Marfan syndrome are living longer and healthier lives, with fewer and less severe complications. Interestingly, along with longer life spans come new issues of aging with this chronic and progressive condition.

• Video: Dr. Nancy Snyderman spotlights the life of a girl on The Today Show, “Understanding Marfan Syndrome”
• Resource: National Marfan Foundation
• Read More: Practical and detailed info about life and issues surrounding Marfan Syndrome

* Interesting note: Clinical discoveries take time. They don’t happen overnight. On May 8, NPR reported on the promise of the blood pressure drug, Losartan to treat Marfan syndrome, spotlighting a boy named Blake Althaus. Two years earlier, in April 2006, NPR reported on promising mouse research, which led the way for human clinical trial later that year that Blake is participating in. At that time, Dr. Hal Dietz of Johns Hopkins said, “The effect in the mice was so dramatic that it’s led to some degree of optimism that this will translate to people.” Today, Dietz “cautions patients that the drug might not work for everyone and that he doesn’t think it will fix everything. But at the same time, things look promising…. He tells his patients that the trial is the only way they can really see what the drug does, find the right dose and identify any side effects.”

Hunter Syndrome is one of several hereditary metabolic conditions known collectively as lysosomal storage disorders. These are genetically distinct diseases that result from a deficiency of a particular enzyme.

• Hunter syndrome, also known as mucopolysaccharidosis II or MPS II, is caused by an inherited deficiency in the enzyme iduronate-2-sulfatase (or I2S). Lack of this enzyme affects the body’s ability to break down and recycle cellular waste.
• Hunter syndrome affects approximately 1 in every 155,000 people. (more…)

Charcot-Marie-Tooth disorder is one of the most common inherited neurological disorders – it affects 1 in 2,500 people in the U.S. This label actually refers to a group of related conditions that affect the body’s peripheral nerves, resulting in pain and muscle weakness in the feet and legs.Until now, the genetic causes for 70% of Charcot-Marie-Tooth cases have been known and genetic testing can help guide treatment for affected individuals. It can also help family members determine their risk.

Now another 5% or so of these families will be able to identify their genetic cause of Charcot-Marie-Tooth. Geneticist Miriam Meisler and her team at the University of Michigan have identified a mutation in a gene (FIG4) in both mice with similar symptoms and people who have Charcot-Marie-Tooth disorder. We can expect this discovery will lead to new strategies for treating the symptoms of this form of the disorder.

(Photo: Mouse with FIG4 mutation, thanks to Miriam Meisler)

Read more on this discovery:

• UMHS press release
• Nature abstract

Anyone looking for information on genetic diseases will be thankful for Scienceroll’s advice on “how to search for genetic conditions”. This list of Top 10 Sites is wonderful list for students, scholars, clinicians and people seeking diagnosis.

Here’s the inspiration behind his top 10 post:

Some months ago, I wrote about Juan Magdaraog who is blogging about his struggle with Pompe disease, a rare, but important genetic condition. He let me know about an essential problem: the diagnostic delay. … Look, we can’t expect physicians (from any kind of medical specialties) to know everything about all the cc. 4000 genetic conditions. But we can help them how to find relevant information and quickly understandable material on genetic conditions.

Thanks for the tips, Berci! Most of these sites live in my bookmarks, but your post reminded me that the goal of making genetics accessible means making our process transparent, too — the tools, the references, the analysis.

Technorati Tags: search, genetics, diseases, conditions, tips, top 10, websites, scienceroll

On Sunday, the NY Times ran an amazing interview/profile of a young woman who, at age 23, decided to be tested for Huntington’s disease: “Facing Life with a Fatal Gene.” By sharing her personal story and much more in such a large forum, Ms. Moser (the young woman) and the journalist, Amy Harmon, have brought awareness and education for HD into the public eye.

Technorati Tags: huntington’s disease, hd, genetic disease, genetic testing, pros and cons

Mayo Clinic researchers have discovered a protein interaction that may explain how the deadly Huntington’s disease affects the brain.

The findings…show how the mutated Huntington’s protein interacts with another protein to cause dramatic accumulation of cholesterol in the brain. “Cholesterol is essential for promoting the connection network among brain cells and in maintaining their membrane integrity. Both the level of cholesterol and its delivery to the proper locations in the cell are essential for the survival of neurons,” explains Mayo Clinic molecular biologist Cynthia McMurrary, Ph.D.

“Our discovery that the mutant Huntington’s disease protein derails the cholesterol delivery system and causes cholesterol accumulation in neurons provides us with key results and solid clues to the mechanism of this disease,” says Dr. McMurray. “Fully understanding the mechanism of toxicity is the key to developing treatments.”

• Read more about this discovery at Science Daily News and from Pure Pedantry
• Learn more about the genetics behind Huntington’s disease in Hsien Lei’s Chromosome Parade
• Newsweek recently profiled a family who used PGD to avoid passing Huntington’s disease on to their children

Technorati Tags: huntington’s disease, research, cholesterol, protein, treatment

In October, I posted about how rescue workers from the World Trade Center were being diagnosed with Alpha-1, an inherited lung and liver disease that is suspected to be much more prevalent than once thought. You don’t hear about Alpha-1 very often — but now there’s encouraging news about a potential treatment for Alpha-1.

A clinical trial at the University of Florida has evaluated a gene therapy to treat Alpha-1 antitrypsin deficiency, and the results are promising. People with Alpha-1 antitrypsin deficiency make little or none of the alpha-1 antitrypsin protein, which is essential for health. In this clinical trial, the researchers used a virus to deliver a corrective gene that codes for the alpha-1 antitrypsin protein to 12 participants with Alpha-1 antitrypsin deficiency. (more…)

Most people haven’t heard of Rett Syndrome, a neurodevelopmental disorder that affects primarily girls. The disease is unfamiliar because it was only in 1983 that Rett syndrome first began appearing in medical literature. Before this time (and still sometimes now), those with Rett syndrome were likely misdiagnosed with autism or cerebral palsy.

One of the hardest parts of Rett syndrome is that girls have normal development for the first 6 to 18 months and then their development plateaus. Gradually, they begin to lose motor function, lose the ability to speak, develop uncontrollable hyperventilation and seizures, develop scoliosis, and regress developmentally in other ways as well. Many of these difficulties stem from apraxia, which is the condition where the girl’s body cannot do what her brain tells it to do.

Rett syndrome occurs approximately once in 8,000 female births, but these numbers may be on the low end. The International Rett Syndrome Assocation (IRSA) notes that there may be hundreds of thousands of girls and women with Rett syndrome throughout the world who are misdiagnosed or unidentified. (more…)

Sounds like the WTC rescue workers who have had serious lung disease problems have a genetic disorder that increases risk of COPD and lung disease when combined with environmental factors (such as smoke, particulates and the like). This condition, called Alpha-1 Antitrypsin Deficiency, is suspected as being as one of the biggest unknown, and underdiagnosed, genetic conditions.

Since DNA Direct has Alpha-1 testing services, I’m going to let an article from Medical News Today tell you about why this is big news: (more…)

Congratulations to our Medical Director, Dr. Kate Rauen, and her team of researchers. Their recent discovery of the genetic basis for cardio-facio-cutaneous (CFC) syndrome continues to receive attention from the medical community.

UCSF Today has an article (with great imaging) about the promise Kate’s research holds:

[u]nlike Down syndrome, many instances of developmental delay are due to small mutations in DNA. These small mutations often consist of no more than a single missing or substituted letter within the string of DNA alphabet building blocks that make up long sequences of genetic code.

(more…)

In July, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) held a Celiac Disease Awareness Campaign to tell the public about this disease that affects an estimated 1 percent of all Americans. Lisa’s previous post gives a summary of the symptoms of celiac disease and coping strategies.

The main message is this: people with celiac disease exhibit an autoimmune response to gluten, which is a protein found in wheat, rye, and barley. There are both genetic and non-genetic (environmental) factors involved in acquiring celiac disease, evidenced by the fact that 70% of identical twins both have celiac disease (since the concordance is not 100%, it is known that there are environmental factors involved as well). According to some gastroenterologists, first-degree relatives of someone with celiac disease are recommended to get endomysial antibody blood tests. (more…)

Have you ever wondered why harmful genetic mutations remain in the gene pool? A mutation in the beta-globin gene provides an example of how a genetic mutation can both help you and hurt you.

With one copy of the mutated gene: individuals are protected against malaria, which is a selective advantage (and so this mutation is sure to stay in the gene pool).

With two copies of the mutated gene, one copy inherited from each parent: individuals develop the harmful genetic disorder called Sickle Cell Anemia.

Sickle cell anemia predominantly affects African Americans because of their recent ancestry in malaria-stricken areas, where it was beneficial to carry one copy of the mutated gene. The disease affects about 1 in 250 - 600 African Americans, but can be found in people of any ethnic background including people of Mediterranean, Middle Eastern, Indian, Central and South American ancestry. (more…)

Have you heard of celiac disease? Most people haven’t, but knowing about it could change the lives of many who suffer from undiagnosed intestinal distress. That’s why yesterday the NIH launched a Celiac Awareness Campaign.

Celiac disease is an autoimmune response to gluten, a protein found in wheat, rye, and barley. Symptoms vary, and they range from gas, diarrhea and abdominal pain, to delayed growth, certain skin rashes, infertility and osteoporosis. Some people develop symptoms as children, others after an event such as an infection, a physical injury, pregnancy, severe stress or surgery.

Celiac disease is commonly under- or misdiagnosed, because its symptoms are similar to those of other diseases. Celiac disease may be confused with irritable bowel syndrome (IBS), iron-deficiency anemia, ulcers, Crohn’s disease, diverticulitis, intestinal infections, and chronic fatigue syndrome (CFS).

(more…)

I’m a bit late in announcing this but the latest issue of Mendel’s Garden, the new genetics blog round-up, is up at Genetics and Health. A few of the selections about rare genetic conditions caught my attention.

Dr. Paul discusses an intriguing collaboration between dog breeders and human researchers. Batten Disease, is a rare genetic disorder that appears in both humans and Tibetan Terriers. The breed club has a DNA database for the dogs, and you can guess the rest — but you really should read Dr. Paul’s commentary about what a collaboration like this can mean for a rare disease.

Filipina Soul writes about a rare, recessive genetic disorder, maple syrup urine disease, and recent research that suggests high carrier rates (up to 1 in 100) among Filipinos. According to Filipina Soul, the researchers have also identified a unique founder mutation that causes the disease. Research such as this is exciting — it can make pre-conception carrier testing possible, not to mention how awareness of ethnic risk increases the likelihood of early postnatal diagnosis.

Over at Ideas for Women, Trisha has thoughtful commentary on a study I’ve been meaning to write about. Recently, the Journal of Clinical Oncology published a preliminary study suggesting that women with BRCA1 or BRCA2 mutations who are exposed to X-rays have a greater risk for breast cancer. (Trisha also reported on the discovery of a BARD1 variant that in combination with a BRCA1 mutation significantly increases cancer risk. This variant has been found only in European families to date.) This has nothing to do with rare genetic conditions, per se, but I share her perspectives about this research, how the media covers news like this, and how we as individuals make choices based on this.

Technorati Tags: mendel’s garden, genetic disorders, batten disease, tibetan terriers, maple syrup urine disease, msud, carrier testing, brca1, brca2, bard1, breast cancer, x-rays