Rare Condition in Infant Diagnosed by Sequencing Exome

Only about one percent of the human genome serves as blueprints for protein production. Mutations in these protein-coding regions can alter a protein's function or prevent it from being made at all--often with significant effects on health. For this reason, 85 % of mutations known to have major clinical effects occur in this small portion of the genome.

Starting with DNA from a blood sample from the patient--an infant in Turkey who was persistently dehydrated and failing to gain weight--the scientists found a gene mutation known to affect electrolyte transport in the intestines and cause a condition called congenital chloride diarrhea. Doctors in Turkey confirmed the diagnosis clinically and were able to provide a treatment tailored to the disease.

The team of Howard Hughes Medical Institute (HHMI; Chevy Chase, MD, USA) scientists led by Prof. Richard Lifton, M.D., Ph.D., chairman department of genetics at Yale School of medicine (New Haven, CT, USA) used a method they had developed for sequencing the exome to discover the gene mutation responsible for the infant's disease

"There have been questions about whether one would be able to accurately, comprehensively and quickly identify mutations in the genome using these approaches, and moreover whether one would then be able to make clinical sense of the resulting data. In this first case, we have demonstrated the utility of this technology, underscoring the potential for its broad use in the clinic," Prof. Lifton said. "As the cost of DNA sequencing continues to plummet, it seems clear that this technology will be useful for clinical diagnosis in a number of settings."

The method and diagnosis were reported in an advanced online publication of the U.S. Proceedings of the National Academy of Sciences (PNAS) on October 19, 2009.

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Howard Hughes Medical Institute
Yale School of medicine