Novel CLCN7 mutation identified in a Han Chinese family with autosomal dominant osteopetrosis-2.
Osteopetrosis is a heritable bone condition featuring increased bone density due to defective osteoclastic bone resorption. Exome sequencing and Sanger sequencing were conducted in Han Chinese family members, some of whom had typical osteopetrosis, and a novel missense variant c.2350A>T (p.R784W) in the chloride channel 7 gene (CLCN7) was identified. This variant cosegregated with the disorder in the family but was not observed in 800 controls. The data indicate that exome sequencing is a powerful and effective molecular diagnostic tool for detecting mutations in osteopetrosis, which is a genetically and clinically heterogeneous disorder. This discovery broadens the CLCN7 gene mutation spectrum and has important implications for clinical therapeutic regimen decisions, prognosis evaluations, and antenatal diagnoses.
Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, China Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China hdeng008@yahoo.com yiguo0816@yahoo.com.
Hao
H
Deng
Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, China.
Dan
D
He
Department of Radiology, the Third Xiangya Hospital, Central South University, Changsha, China.
Pengfei
P
Rong
Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, China.
Hongbo
H
Xu
Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, China.
Lamei
L
Yuan
Department of Pediatrics, the Third Xiangya Hospital, Central South University, Changsha, China.
Liu
L
Li
Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, China.
Qian
Q
Lu
Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, China Department of Medical Information, Information Security and Big Data Research Institute, Central South University, Changsha, China.
Yi
Y
Guo
D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D018118:Chloride Channels / Q000737:chemistry / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics*; D059472:Exome / Q000235:genetics; D005190:Family; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010022:Osteopetrosis / Q000000981:diagnostic imaging / Q000235:genetics*; D010375:Pedigree
C097540:CLCN7 protein, human; D018118:Chloride Channels
Autosomal dominant osteopetrosis-2; exome sequencing; mutation; the CLCN7 gene