Genetic screening of EXT1 and EXT2 in Cypriot families with hereditary multiple osteochondromas.

Abstract

The purpose of this study was to perform genetic screening of the exostosin 1 (EXT1) and exostosin 2 (EXT2) genes in Cypriot patients with a clinical diagnosis of hereditary multiple osteochondromas (HMO). Initially, mutation analysis of the EXT1 gene was performed by Sanger sequencing. When no point mutation was identified in EXT1, EXT2 analysis was performed. When no sequence variant was identified in either of the candidate genes, array-comparative genomic hybridization (CGH) was implemented to detect any large copy number changes (CNCs). In total, three point mutations and a large deletion were identified in EXT1: the c.2101C>T(p.Arg701*) mutation and the ∼0.16-Mb deletion removing exons 2–11, which were previously reported whereas the c.486_489delCAGA(p.Asp162Glyfs*12) and the c.868G>T(p.Glu290*) mutations which were novel. It is the first report on genetic screening of five HMO patients of Cypriot descent. The observations presented provide additional evidence for the variability in phenotypic expression and the mutational spectrum of this disorder. The term HMO, or hereditary multiple exostoses (HME), MIM: 133700 and MIM: 133701 respectively is used to describe a genetic disorder characterized by the development of multiple, circumscript, occasionally painful and usually symmetric bony protuberances called osteochondromas (benign cartilaginous tumours which most frequently grow outward from the juxtaphyseal region of the long bones or