{"doi":"10.1210/clinem/dgae040","title":"Autosomal Dominant Osteopetrosis (ADO) Caused by a Missense Variant in the <i>TCIRG1</i> Gene","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.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2024,"id":454000,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9624,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":434027,"name":"Amy J. Katz","orcid":"0000-0003-0846-0725","position":1,"is_corresponding":false},{"id":1277667,"name":"Marian Hart","orcid":null,"position":2,"is_corresponding":false},{"id":389978,"name":"Stuart J. Warden","orcid":"0000-0002-6415-4936","position":3,"is_corresponding":false},{"id":389977,"name":"Paul Niziolek","orcid":"0000-0003-4391-7508","position":4,"is_corresponding":false},{"id":798099,"name":"Imranul Alam","orcid":"0000-0002-8914-0610","position":5,"is_corresponding":false},{"id":1277255,"name":"Steven Ing","orcid":"0000-0002-4343-6723","position":6,"is_corresponding":false},{"id":422116,"name":"Lynda E. Polgreen","orcid":"0000-0002-2881-6138","position":7,"is_corresponding":false},{"id":382681,"name":"Erik A. Imel","orcid":"0000-0002-7284-3467","position":8,"is_corresponding":false},{"id":85475,"name":"Michael J. Econs","orcid":"0000-0003-0940-1911","position":9,"is_corresponding":false},{"id":1277254,"name":"Wade Jodeh","orcid":"0000-0002-2887-0513","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T02:03:07.923686Z","pmid":"38261998","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}