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

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

Author information

1
a Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Disease , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China.

Abstract

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

PMID:
28975865
DOI:
10.1080/00325481.2017.1386529
[Indexed for MEDLINE]

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