In the Foye household in Pine Brook, N.J., a biomedical twist on an Advent calendar went up on the fireplace mantle in early October: a countdown to the long-awaited day they would find out what gene caused 11-year-old Adam Foyes mysterious and rare muscle-weakening disease.

Each day, a different family membermom, dad, Adam, grandmapulled off a numbered sticky note, ticking off the days until a mid-October conference call. That day, the family got a precious answer, learning the fruits of a contest organized by Boston Childrens Hospital. Twenty-three teams of scientists from around the world had combed through the DNA blueprints of Adam and his parents, Sarah and Patrick, to try and understand why Adam tired so easily, needing a scooter to walk longer than a few blocks and requiring a ventilator to help him breathe at night.

What they found was that Adams disease, called centronuclear myopathy, stemmed from mutations in a giant gene called titin.

It answers so many questions, said Sarah Foye. You have a child with this disorder, and everyday I look at him and hes too tired to play and too tired to go to school. I always ask what is it, what is causing this, and what can I do to help.

Identifying the gene is only a first step, but an important one. Researchers at Boston Childrens have a zebrafish with the same gene mutations that will allow them to screen for drugs that might help Adam. The finding, however, also suggests that a potential drug trial that is being developed for a similar condition would not work for Adam, knowledge that will spare him the unnecessary treatments that often come with downsides.

We can now say that drug has virtually no chance of working, which is disappointing on one level, but is also an important result because every drug has side effects, and Adam can be spared those, said Alan Beggs, director of the Manton Center for Orphan Disease Research at the hospital and a co-organizer of the contest.

Beyond the solace provided to the Foye family, the contest aimed to provide new thinking on how to deal with many of the problems that come with the unprecedented amount of personal information provided by DNA-sequencing technologies. As the cost of obtaining a persons genome plummets, scientists and clinicians are wrestling with how to extract meaning from such large amounts of data, how to present it in a comprehensible way to physicians and patients, and how to best handle incidental findings that might emerge when studying the genome.

The dilemma now is to identify the key changes, or mutations, that are responsible for the patients medical condition, and determine which they are against this background of enormous normal variation in human DNA sequences, Beggs said. The purpose of the challenge was to develop best practices for the interpetation and return of these new types of data to patients physicians.

The winner of a $15,000 prize was the Division of Clinical Genetics at Brigham and Womens Hospital. Teams were given the full genome sequences from three families. Each had a child with a rare genetic disease that stemmed from an unknown cause, and teams took on the massive challenge of pinpointing the probable cause of their muscle weakness or cardiac defects, but also addressing other issues that arise when sequencing the genome.

For example, the teams wrote up reports that could be provided to physicians that would allow them to explain the genetic mutation to each patients family. Some teams provided samples of the consent form they would ask a patient and family members to sign before providing their DNA to doctors, requesting, for example, whether they would want to receive incidental informationsuch as the risk for another kind of illness that might lie in their genes, but was not the focus of the study.

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Boston Children’s Hospital contest pinpoints the gene that causes a muscle-weakening disorder

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