Autosomal Dominant Osteopetrosis (ADO) Caused by a Missense Variant in the TCIRG1 Gene
dc.contributor.author | Jodeh, Wade | |
dc.contributor.author | Katz, Amy J. | |
dc.contributor.author | Hart, Marian | |
dc.contributor.author | Warden, Stuart J. | |
dc.contributor.author | Niziolek, Paul | |
dc.contributor.author | Alam, Imranul | |
dc.contributor.author | Ing, Steven | |
dc.contributor.author | Polgreen, Lynda E. | |
dc.contributor.author | Imel, Erik A. | |
dc.contributor.author | Econs, Michael J. | |
dc.contributor.department | Medicine, School of Medicine | |
dc.date.accessioned | 2025-02-18T08:22:52Z | |
dc.date.available | 2025-02-18T08:22:52Z | |
dc.date.issued | 2024 | |
dc.description.abstract | Context: Autosomal dominant osteopetrosis (ADO) is a rare genetic disorder resulting from impaired osteoclastic bone resorption. Clinical manifestations frequently include fractures, osteonecrosis (particularly of the jaw or maxilla), osteomyelitis, blindness, and/or bone marrow failure. ADO usually results from heterozygous missense variants in the Chloride Channel 7 gene (CLCN7) that cause disease by a dominant negative mechanism. Variants in the T-cell immune regulator 1 gene (TCIRG1) are commonly identified in autosomal recessive osteopetrosis but have only been reported in 1 patient with ADO. Case description: Here, we report 3 family members with a single heterozygous missense variant (p.Gly579Arg) in TCIRG1 who have a phenotype consistent with ADO. Three of 5 protein prediction programs suggest this variant likely inhibits the function of TCIRG1. Conclusion: This is the first description of adult presentation of ADO caused by a TCIRG1 variant. Similar to families with ADO from CLCN7 mutations, this variant in TCIRG1 results in marked phenotype variability, with 2 subjects having severe disease and the third having very mild disease. This family report implicates TCIRG1 missense mutations as a cause of ADO and demonstrates that the marked phenotypic variability in ADO may extend to disease caused by TCIRG1 missense mutations. | |
dc.identifier.citation | Jodeh W, Katz AJ, Hart M, et al. Autosomal Dominant Osteopetrosis (ADO) Caused by a Missense Variant in the TCIRG1 Gene. J Clin Endocrinol Metab. 2024;109(7):1726-1732. doi:10.1210/clinem/dgae040 | |
dc.identifier.uri | https://hdl.handle.net/1805/45764 | |
dc.language.iso | en_US | |
dc.publisher | Oxford University Press | |
dc.relation.isversionof | 10.1210/clinem/dgae040 | |
dc.relation.journal | The Journal of Clinical Endocrinology and Metabolism | |
dc.rights | Publisher Policy | |
dc.source | PMC | |
dc.subject | Autosomal dominant osteopetrosis | |
dc.subject | TCIRG1 | |
dc.subject | Missense | |
dc.subject | Variant | |
dc.title | Autosomal Dominant Osteopetrosis (ADO) Caused by a Missense Variant in the TCIRG1 Gene | |
dc.type | Article | |
ul.alternative.fulltext | https://pmc.ncbi.nlm.nih.gov/articles/PMC11180502/ |