A recent study shows that whole-exome sequencing can be used to diagnose genetic defects in patients with a range of phenotypes (NEJM 2013; 369: 1502-11).
In this study, the first 250 patients who had whole-exome sequencing performed at Baylor College of Medicine were studied. 80% had neurological problems and all had undergone previous extensive evaluation.
Results:
- The authors identified “86 mutated alleles that were highly likely to be causative in 62 patients (25%)”
- 83% of the autosomal dominant mutant alleles (n=33) and 40% of the X-linked mutant alleles (n=9) occurred de novo.
- In four patients, the authors identified multiple causative genes. This may lead to a paradigm shift from Occam’s razor towards more cases of “multiple hits.”
- The authors speculate that the yield of this type of testing will improve as databases grow since many mutations at this time are of uncertain clinical significance
Bottomline: While this approach was used mainly in individuals with unexplained neurological problems, the use of whole-exome sequencing has broad potential. In GI/Liver, the uses could include unexplained diarrheal disorders, metabolic/cholestatic liver disease, failure to thrive, inflammatory bowel disease, and many other conditions.
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