Assessing the general population frequency of rare coding variants in the EXT1 and EXT2 genes previously implicated in hereditary multiple exostoses.

ABSTRACT: Hereditary multiple exostoses (HME) is a rare childhood-onset skeletal disease linked to mutations in exostosin glycosyltransferase 1 (EXT1) or 2 (EXT2). Patients are heterozygous for either an EXT1 or EXT2 mutation, and it is widely assumed that exostosis formation and associated defects, such as growth retardation and skeletal deformities, require loss-of-heterozygosity or a second hit in affected cells. However, the relevance and phenotypic impact of many presumed pathogenic EXT variants remain uncertain. We extracted all amino acid-altering (missense) and loss of function (LoF; nonsense, frameshift, or splice-site) variants from the Exome Aggregation Consortium (ExAC), a large population-based repository of exome sequence data from diverse ancestries that has screened out severe pediat

SUBMITTER: Cousminer DL 

PROVIDER: S-EPMC5056851 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature