Case Report
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jan 26, 2023; 11(3): 700-708
Published online Jan 26, 2023. doi: 10.12998/wjcc.v11.i3.700
Clinical and genetic diagnosis of autosomal dominant osteopetrosis type II in a Chinese family: A case report
Hong-Ping Gong, Yan Ren, Pan-Pan Zha, Wen-Yan Zhang, Jin Zhang, Zhi-Wen Zhang, Chun Wang
Hong-Ping Gong, International Medical Center Ward, General Practice Medical Center, Sichuan University West China Hospital, Chengdu 610041, Sichuan Province, China
Hong-Ping Gong, Yan Ren, Pan-Pan Zha, Chun Wang, Department of Endocrinology and Metabolism, Sichuan University West China Hospital, Chengdu 610041, Sichuan Province, China
Wen-Yan Zhang, Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Jin Zhang, Zhi-Wen Zhang, Department of Endocrinology and Metabolism, The People’s Hospital of Leshan, Leshan 614003, Sichuan Province, China
Author contributions: Gong HP and Ren Y wrote the manuscript; Gong HP, Ren Y and Wang C revised the manuscript; Gong HP, Ren Y, Zha PP, Zhang J and Zhang ZW contributed to the collection of the clinical data; Zhang WY performed a histopathological review and pathological diagnosis of this case was performed independently; all authors contributed to and approved the final manuscript for publication.
Supported by the Science and Technology Plan Program of Sichuan of China, No. 2018JY0608.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Chun Wang, Doctor, PhD, Chief Doctor, Department of Endocrinology and Metabolism, Sichuan University West China Hospital, No. 37 Guoxue Lane, Chengdu 610041, Sichuan Province, China.
Received: November 23, 2022
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

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.

Keywords: Osteopetrosis, Autosomal dominant osteopetrosis type II, Diagnosis, Genetic analysis, Case report

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.