Molecular Genetic Study of Multiple Hereditary Exostoses in the EXT2 Gene

Abstract

Multiple hereditary exostoses (MHE) is a genetically heterogeneous disease with an autosomal dominant type of inheritance, a very large proportion of family cases. The incidence of the disease in various Caucasian populations is from 1.3 to 2 per 100 thousand. The clinical picture is characterized by the presence of multiple cartilaginous outgrowths in the metaphysics of long tubular bones. The most common variant is mutations in EXT genes. For the first time in the Republic of Sakha (Yakutia), a molecular genetic analysis of multiple exostosis chondrodysplasia was carried out. We investigated 57 patients from 31 unrelated families with a clinical diagnosis of MECHD by mass parallel sequencing (MPS) for all coding EXT2 regions followed by validation of results by direct Sanger sequencing. As a result, frequent major mutations c.409delA (p.Ile137fs), c.751C > T (p.Gln251 *) in the ЕХТ2 gene in Yakuts were revealed.