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 Tcell 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.