DNA sequencing is an important tool for discovering the cause of rare diseases.

According to the National Organization of Rare Disorders (NORD), there are nearly 7,000 rare diseases that affect nearly 30 million Americans, or approximately one in ten Americans. Eleven-year-old Adam Foye from New Jersey is among this group. Adam suffers from a condition known as centronuclear myopathy; fewer than fifty affected families have been reported in scientific journals.

Patients with centronuclear myopathy suffer from progressive muscular weakness, which can create numerous challenges, including the need for a wheelchair and a ventilator. Some patients also may have life-threatening heart problems.

Because of their scarcity, the correct diagnosis of rare diseases can take many years and effective treatments are few. Now, thanks to an international contest sponsored by Boston Children’s Hospital, Adam and his family have new insight into the possible cause of Adam’s disease. This insight may lead to improved care for Adam and other rare disease patients.

The contest, known as the Children’s Leadership Award for the Reliable Interpretation and appropriate Transmission of Your genomic information (CLARITY), challenged 30 teams of researchers to solve the medical mysteries of three families, including Adam and his family, by studying their genes through a process called DNA sequencing. The teams were asked to interpret and analyze the DNA sequences of the samples and communicate their results in a way that would help physicians easily explain the results to patients and their families.

Led by Dr. Shamil Sunyaev from the Brigham and Women’s Hospital (BWH) Division of Genetics, the winning team found that Adam’s condition is likely related to mutations in a gene called titin, the largest gene in the human genome. (This finding was consistent with independently conducted research by other scientists who studied larger patient groups.) The work of the BWH-led research team, which included scientists from the Division of Genetics, Massachusetts General Hospital, Partners Laboratory for Molecular Medicine, Brown University and Utrecht University, Netherlands, was considered to have the best combination of clarity and usefulness for the three families.

Sunyaev and his team plan to refine their work.  “We hope to come up with a table of the most important things to consider in the interpretation of genomic data, and share this information,” said Sunyaev.  “This could streamline the analysis of future cases; hopefully others could also benefit from our tools of analysis.”

Finding the possible gene responsible for Adam’s disorder is a first step in developing a treatment. The possible link to the titin gene is also important because it has been associated with heart problems, suggesting that cardiac monitoring of Adam’s condition may be helpful.

The CLARITY team is planning a second challenge later this year on the interpretation of cancer genomes.

You can learn more about rare diseases and resources for patients and families, including the upcoming Rare Disease Day on February 28, 2013, at the following sites:

– Jamie R, Michelle C


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