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t m c » p u l s e | s e p t e m b e r 2 0 1 5 17 exhaustive state-of-the-art testing: CTs, MRIs, lumbar punctures and repeated lab workups that perpetually came back negative. For over three years they tried to identify the cause of his developmental regression, while Jacob's condition worsened. Despite brief misdiagnoses, visits with specialists from coast to coast and multiple lifestyle changes, nobody could explain what had happened. Then, in 2013, a genetic counselor at Baylor called to tell Phillips about the breakthroughs in whole exome sequencing. Jacob, she said, was a perfect candidate. By August of that year, the Phillips family finally had a clear diagnosis: Jacob was suffering from an extremely rare genetic disorder called infantile neuroaxonal dystrophy, a neurodegenerative disease caused by a mutation in the PLA2G6 gene. Through impaired function of necessary enzymes, the mutation causes progressive neurodegeneration, explaining Jacob's lapsed motor skills and reduced mobility. The condition is so rare that in 2013, Jacob was only the 10th child in the U.S. to have been diagnosed with the disease. His case is also unique—as a rule, both parents must be carriers for the mutation to be passed on to the child, but in Jacob's case, only his mother tested positive for the recessive mutation. Geneticists believe the gene somehow mutated independently or was double-copied from her chromosome. Unfortunately, there is no known cure for the disorder, which, like other neurodegenerative diseases such as Parkinson's or Alzheimer's, continues to advance as time passes. Jacob is now six years old and in hospice care—he is 95 percent blind, nonverbal and has lost all motor skills. Still, his parents remain hopeful. Since his diagnosis in 2013, they have raised enough funds to fully support two different research projects for the disease, one of which is exclusively focused on gene therapy, a promising new technique that harnesses genes to treat genetic disorders. While there is no guarantee that either will produce a treatment or cure, the value of the diagnosis itself cannot be underestimated. "Before the diagnosis, we thought it was everything under the sun," said Phillips. "For so long we believed his condition had been directly caused by the virus, and although we suspect that may have been an environmental trigger for the disorder, at least now we know what we're working with. We know what to expect and how to manage his pain, and we're able to move forward as far as the research goes. Without the diagnosis, there would have been no hope, no chance for his survival. At least now, through our research, there's that possibility." "If you are a parent or a family in that situation, the impact of a diagnosis is huge," said Gibbs. "When you are able to resolve this down to a genetic cause, you provide prediction, you provide a peer group, and you accentuate the pathway to therapeutics, which is the most active area of research right now. You can't underestimate the value of diagnostics and prognostics. We've got to understand all the basic nuts and bolts before we can fix what's broken." Nowhere is the value of collecting and understanding data—the basics of how the genes actually function—potentially more significant than in the field of cancer research. At its core, genetic diagnostics winnows down to basic discovery and understanding. A child who has a single gene defect indicates the function of that gene—if there is a mutation in the gene, the protein the gene codes for is altered or missing, and those effects tell scientists what the protein normally does. That's genomics 101, and in cancer cells the same comparison can be made between cancer tissue and non-cancerous normal tissue. We have this global mission and vision that ultimately, every person who has any health issue should have a genome sequence as part of their work-up, just as they would have an X-ray or metabolite test. — RICHARD GIBBS, PH.D. Director of the Human Genome Sequencing Center at Baylor College of Medicine The genomics laboratory at Baylor College of Medicine has been at the forefront of designing cutting-edge technology for quicker, more accurate, and less expensive DNA sequencing.