Identification of a novel LDLR mutation (c.261_262invGA, p.Trp87X): Importance of specifying DNA and protein mutations.

ClinSeq is a large-scale medical sequencing (LSMS) project at the National Institutes of Health (NIH), the goal of which is to pilot the feasibility of using high throughput genome sequencing for clinical research and eventually to improve the delivery of healthcare. In phase one, 1000 participants are being clinically evaluated for cardiovascular phenotypes and DNA is being collected for sequencing of 400 candidate genes to identify genetic variants that may predispose to the early development of atherosclerosis. We report on an individual with familial hypercholesterolemia (OMIM #143890) who has a novel mutation, c.261_262invGA that predicts a premature stop (p.Trp87X) in the LDLR gene. Although the p.Trp87X predicted protein mutation has been reported, c.261_262invGA is distinct from mutations reported in prior families and emphasizes the importance of describing mutations at the DNA level. It is important to describe mutations according to the underlying DNA change as multiple nucleotide changes may underlie a single predicted protein change.