Autosomal dominant osteopetrosis type II resulting from a de novo mutation in the CLCN7 gene: A case report

Abstract

Background: Osteopetrosis is a family of extremely rare diseases caused by failure of osteoclasts and impaired bone resorption. Among them, autosomal dominant osteopetrosis type II (ADO II), related to the chloride channel 7 (CLCN7) gene, is the most frequent form of osteopetrosis. In this study, we report a de novo mutation of CLCN7 in a patient without the family history of ADO II.

Case summary: A 5-year-old Chinese boy with ADO II was found to have a de novo mutation in the CLCN7 gene [c.746C>T (p.P249L)]. Typical clinical manifestations, including thickening of the cortex of spinal bones and long bones, non-traumatic fracture of the femoral neck, and femoral head necrosis, were found in this patient. The patient is the first reported case of ADO II with the missense mutation c.746C>T (p.P249L) of the CLCN7 gene reported in China. We also review the available literature on ADO II-related CLCN7 mutations, including baseline patient clinical features, special clinical significance, and common mutations.

Conclusion: Our report will enrich the understanding of mutations in ADO II patients. The possibility of a de novo mutation should be considered in individuals who have no family history of osteopetrosis.

Keywords: Autosomal dominant osteopetrosis type Ⅱ; Case report; Chloride channel 7 gene; Osteopetrosis; Whole exome sequencing.

Figure 1

Diagnostic process. A-C: Pelvis X-ray (A), magnetic resonance imaging (B), and computed tomography (C) showed thickening of the cortex and narrowing of the medullary cavity in the pelvis and bilateral femurs. The neck of the right femoral head was irregular in shape and showed some free small bone shadow, suggesting the possibility of right femoral head and neck fracture (orange arrows); D and G: X-rays of the chest and right femur showed extensive bone density in the thoracic vertebrae, lumbar vertebrae, bilateral ribs, and bilateral humerus. There were no obvious abnormalities in the lungs, heart, or septum; E and F: Sanger sequencing to verify the heterozygous mutation of the CLCN7 gene (c.746C>T)