Early diagosis of Werner's syndrome using exome-wide sequencingin a singe, atypical patient

Abstract

Genetic diagosis of inherited metabolic disease is conventionally achieved throug syndrome recogition and targted gne sequencing but many patients receive no specific diagosis. Next-gneration sequencingallied to capture of expressed sequences from gnomic DNA now offers a powerful new diagostic approach. Barriers to routine diagostic use include cost, and the complexity of interpretingresults arisingfrom simultaneous identification of larg numbers of variants. We applied exome-wide sequencingto an individual, 16-year-old daugter of consangineous parents with a novel syndrome of short stature, severe insulin resistance, ptosis, and microcephaly. Pulldown of expressed sequences from gnomic DNA ..