Published online Jan 26, 2023. doi: 10.12998/wjcc.v11.i3.700
Peer-review started: November 23, 2022
First decision: December 13, 2022
Revised: December 23, 2022
Accepted: January 5, 2023
Article in press: January 5, 2023
Published online: January 26, 2023
Processing time: 64 Days and 3.4 Hours
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.
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.
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.
Core Tip: Autosomal dominant osteopetrosis (ADO-II) is an autosomal dominant form of osteopetrosis. In ADO-II patients, the clinical spectrum ranges from nonsymptomatic to recurrent fractures, anemia, and a favorable prognosis. We reported a 53-year-old female patient with persistent joint pain, who was accidentally diagnosed with ADO-II at a later age. Her asymptomatic daughter was also diagnosed with ADO-II, as confirmed by whole exome sequencing.