Novel mutations of CLCN7 cause autosomal dominant osteopetrosis type II (ADOII) and intermediate autosomal recessive osteopetrosis (ARO) in seven Chinese families

Postgrad Med. 2017 Nov;129(8):934-942. doi: 10.1080/00325481.2017.1386529. Epub 2017 Oct 11.


Objectives: Defects in the chloride channel 7 (CLCN7) gene lead to autosomal dominant osteopetrosis type II (ADOII, OPTA2 MIM 166600) and autosomal recessive osteopetrosis, autosomal recessive 4 (ARO, OPTB4 MIM 611490). The objective of the present study was to expand the mutational spectrum and analyze the correlation between mutational sites and clinical phenotypes.

Methods: Seven affected individuals from unrelated Chinese families were clinically examined. X-ray examination and biochemical markers were evaluated. The 25 exons of CLCN7 and exon-intron boundaries were amplified and analyzed; we also used μ-CT to distinguish the features of sclerotic bone from the great trochanter of Pt 6 using the bones of unaffected subject in vitro.

Results: We identified six cases of OPTA2 and one case of OPTB4. One OPTA2 patient displaying life-threatening symptoms died, and the OPTB4 patient presenting a relatively mild clinical course survived. We identified eight different CLCN7 mutations, including three novel mutations (p.G240E, p.F318S, and p.S753W), and μ-CT analysis showed that the volumetric bone mineral density, total porosity and open porosity of sclerotic bone were higher than the control.

Conclusions: The present study revealed three novel mutations, showed the dense but brittle sclerotic bones of an OPTA2 patient, characterized OPTA2 symptoms from benign to fatal and reported a rare intermediate case of ARO in a Chinese population.

Keywords: ADOII; ARO; CLCN7; Osteopetrosis; μ-CT.

MeSH terms

  • Adolescent
  • Adult
  • Asians
  • Biomarkers
  • Bone Density
  • Child, Preschool
  • China
  • Chloride Channels / genetics*
  • Female
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Osteopetrosis / genetics*
  • Osteopetrosis / physiopathology*
  • Phenotype
  • Young Adult


  • Biomarkers
  • CLCN7 protein, human
  • Chloride Channels

Supplementary concepts

  • Osteopetrosis, Autosomal Recessive 4