Genetic Analysis of CLCN7 in an Old Female Patient with Type II Autosomal Dominant Osteopetrosis

Type II autosomal dominant osteopetrosis (ADO II) is a rare genetically heterogeneous disorder characterized by osteosclerosis and increased bone mass, predominantly involving spine, pelvis, and skull. It is closely related to functional defect of osteoclasts caused by chloride voltage-gated channel 7 ( ) gene mutations. In this study, we aimed to identify the pathogenic mutation in a Korean patient with ADO II using whole exome sequencing. We evaluated the clinical, biochemical, and radiographic analysis of a 68-year-old woman with ADO II. We also performed whole exome sequencing to identify pathogenic mutation of a rare genetic disorder of the skeleton. Moreover, a polymorphism phenotyping program, Polymorphism Phenotyping v2 (PolyPhen-2), was used to assess the effect of the identified mutation on protein function. Whole exome sequencing using peripheral leukocytes revealed a heterozygous c.296A>G missense mutation in the gene. The mutation was also confirmed using Sanger sequencing. The mutation c.296A>G was regarded to have a pathogenic effect by PolyPhen-2 software. We detect a heterozygous mutation in gene of a patient with ADO II, which is the first report in Korea. Our present findings suggest that symptoms and signs of ADO II patient having a c.296A>G mutation in may appear at a very late age. The present study would also enrich the database of mutations and improve our understanding of ADO II.