Genetic Analysis of CLCN7 in an Old Female Patient with Type II Autosomal Dominant Osteopetrosis.
10.3803/EnM.2018.33.3.380
- Author:
Seon Young KIM
1
;
Younghak LEE
;
Yea Eun KANG
;
Ji Min KIM
;
Kyong Hye JOUNG
;
Ju Hee LEE
;
Koon Soon KIM
;
Hyun Jin KIM
;
Bon Jeong KU
;
Minho SHONG
;
Hyon Seung YI
Author Information
1. Department of Laboratory Medicine, Chungnam National University College of Medicine, Daejeon, Korea.
- Publication Type:Original Article
- Keywords:
Type 2 autosomal dominant osteopetrosis;
CLCN7 gene;
Osteosclerosis;
Whole exome sequencing
- MeSH:
Aged;
Exome;
Female*;
Humans;
Korea;
Leukocytes;
Mutation, Missense;
Osteoclasts;
Osteopetrosis*;
Osteosclerosis;
Pelvis;
Skeleton;
Skull;
Spine
- From:Endocrinology and Metabolism
2018;33(3):380-386
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: 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 (CLCN7) gene mutations. In this study, we aimed to identify the pathogenic mutation in a Korean patient with ADO II using whole exome sequencing. METHODS: 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. RESULTS: Whole exome sequencing using peripheral leukocytes revealed a heterozygous c.296A>G missense mutation in the CLCN7 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. CONCLUSION: We detect a heterozygous mutation in CLCN7 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 CLCN7 may appear at a very late age. The present study would also enrich the database of CLCN7 mutations and improve our understanding of ADO II.
