Clinical and genetic diagnosis of autosomal dominant osteopetrosis type II in a Chinese family: A case report

Background: Osteopetrosis is a rare genetic disorder characterized by increased bone density due to defective bone resorption of osteoclasts. Approximately, 80% of autosomal dominant osteopetrosis type II (ADO-II) patients were usually affected by heterozygous dominant mutations in the chloride voltage-gated channel 7 (ClCN7) gene and present early-onset osteoarthritis or recurrent fractures. In this study, we report a case of persistent joint pain without bone injury or underlying history.

Case summary: We report a 53-year-old female with joint pain who was accidentally diagnosed with ADO-II. The clinical diagnosis was based on increased bone density and typical radiographic features. Two heterozygous mutations in the ClCN7 and T-cell immune regulator 1 (TCIRG1) genes by whole exome sequencing were identified in the patient and her daughter. The missense mutation (c.857G>A) occurred in the CLCN7 gene p. R286Q, which is highly conserved across species. The TCIRG1 gene point mutation (c.714-20G>A) in intron 7 (near the splicing site of exon 7) had no effect on subsequent transcription.

Conclusion: This ADO-II case had a pathogenic CLCN7 mutation and late onset without the usual clinical symptoms. For the diagnosis and assessment of the prognosis for osteopetrosis, genetic analysis is advised.