Novel CLCN7 mutations cause autosomal dominant osteopetrosis type II and intermediate autosomal recessive osteopetrosis.

Osteopetrosis refers to a group of rare genetic bone diseases that are clinically characterized by increased bone mass and fragility. The principal pathogenic defect in patients with chloride channel 7 (CLCN7) gene‑dependent osteopetrosis is reduced osteoclast activity, which leads to decreased bone resorption. Mutations in the CLCN7 gene result in autosomal dominant osteopetrosis type II (ADO‑II), autosomal recessive osteopetrosis (ARO) and intermediate ARO (IARO). In the present study, eight mutations in the CLCN7 gene were identified in six patients with familial osteopetrosis and one patient with sporadic osteopetrosis. Heterozygous mutations c.856C>T (R286W), c.2236T>G (Y746D), c.296A>G (Y99C) and c.937G>A (E313K), and a splice mutation (c.2232‑2A>G) in the CLCN7 gene were detected in patients with ADO‑II. A homozygous mutation c.2377G>C (G793R), and a compound heterozygous mutation c.1409C>T (P470L) and c.647_648dupTG (K217X) were detected in two Chinese families with IARO. Among these mutations, two heterozygous mutations (c.2236T>G and c.2232‑2A>G), one homozygous mutation (c.2377G>C) and the compound heterozygous mutation (c.1409C>T and c.647_648dupTG) are novel, to the best of our knowledge. The present findings not only broaden the allelic spectrum of CLCN7 mutations, but also provide increased knowledge of the clinical phenotypes observed in Chinese patients with osteopetrosis.