Clinical and genetic characteristics of osteopetrosis in children.
10.7499/j.issn.1008-8830.2411167
- Author:
Min WANG
1
;
Ao-Shuang JIANG
1
;
Cheng-Lin ZHU
1
;
Jie WANG
1
;
Ya-Ping WANG
1
;
Shan GAO
1
;
Yan LI
1
;
Tian-Ping CHEN
1
;
Hong-Jun LIU
1
;
Jian WANG
1
Author Information
1. Department of Hematology and Oncology, Anhui Provincial Children's Hospital, Hefei 230022, China.
- Publication Type:Journal Article
- Keywords:
CLCN7 gene;
Child;
Gene variant;
Osteopetrosis;
TCIRG1 gene
- MeSH:
Humans;
Osteopetrosis/genetics*;
Male;
Female;
Infant;
Child, Preschool;
Retrospective Studies;
Vacuolar Proton-Translocating ATPases/genetics*;
Child;
Chloride Channels/genetics*;
Mutation;
Receptor Activator of Nuclear Factor-kappa B
- From:
Chinese Journal of Contemporary Pediatrics
2025;27(5):568-573
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To study the clinical and genetic characteristics of osteopetrosis (OPT) in children.
METHODS:A retrospective analysis was performed on the clinical data of 14 children with OPT. Whole-exome sequencing was used to detect pathogenic genes, and clinical phenotypes and genotypic features were summarized.
RESULTS:Among the 14 children (10 males and 4 females), the median age at diagnosis was 8 months. Clinical manifestations included systemic osteosclerosis (14 cases, 100%), anemia (12 cases, 86%), infections (10 cases, 71%), thrombocytopenia (9 cases, 64%), hepatosplenomegaly (8 cases, 57%), and developmental delay (5 cases, 36%). Malignant osteopetrosis (MOP) cases had lower platelet counts, creatine kinase isoenzyme, and serum calcium levels, but higher white blood cell counts, lactate dehydrogenase, and alkaline phosphatase levels compared to non-MOP cases (P<0.05). Genetic testing identified 15 variants in 12 patients, including 8 variants in the CLCN7 gene (53%), 6 in the TCIRG1 gene (40%), and 1 in the TNFRSF11A gene (7%). Three novel CLCN7 variants were identified: c.2351G>C, c.1215-43C>T, and c.1534G>A. All four patients with TCIRG1 variants exhibited MOP clinical phenotypes. Of the seven patients with CLCN7 variants, 4 presented with intermediate OPT, 2 with benign OPT, and 1 with MOP.
CONCLUSIONS:Clinical phenotypes of OPT in children are heterogeneous, predominantly involving CLCN7 and TCIRG1 gene variants, with a correlation between clinical phenotypes and genotypes.
