{"doi":"10.1038/s41431-024-01644-5","title":"STAC3 disorder: a common cause of congenital hypotonia in Southern African patients","abstract":"STAC3 disorder, or Native American myopathy, is characterised by congenital myopathy, hypotonia, musculoskeletal and palatal anomalies, and susceptibility to malignant hyperthermia. A STAC3 c.851 G > C (p.Trp284Ser) pathogenic variant, common in the Lumbee Native American tribe, has been identified in other populations worldwide, including patients of African ancestry. We report on the frequency of STAC3 c.851 G > C in a cohort of 127 patients presenting with congenital hypotonia that tested negative for spinal muscular atrophy and/or Prader-Willi syndrome. We present a clinical retrospective, descriptive review on 31 Southern African patients homozygous for STAC3 c.851 G > C. The frequencies of various phenotypic characteristics were calculated. In total, 25/127 (20%) laboratory-based samples were homozygous for STAC3 c.851 G > C. A carrier rate of 1/56 and a predicted birth rate of 1/12 500 was estimated from a healthy cohort. A common haplotype spanning STAC3 was identified in four patients. Of the clinical group, 93% had a palatal abnormality, 52% a spinal anomaly, 59% had talipes equinovarus deformity/deformities, 38% had arthrogryposis multiplex congenita, and 22% had a history suggestive of malignant hyperthermia. The novel finding that STAC3 disorder is a common African myopathy has important clinical implications for the diagnosis, treatment and genetic counselling of individuals, with neonatal and/or childhood hypotonia with or without arthrogryposis multiplex congenita, and their families. The spread of this variant worldwide and the allele frequency higher in the African/African-American ancestry than the Admixed Americans, strongly indicates that the STAC3 c.851 G > C variant has an African origin which may be due to an ancient mutation with migration and population bottlenecks.","journal":"European Journal of Human Genetics","year":2024,"id":440465,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9588,"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":1252035,"name":"Bronwyn Dillon","orcid":"0000-0001-7560-7307","position":1,"is_corresponding":false},{"id":1252421,"name":"Felicity Mhlongo","orcid":null,"position":2,"is_corresponding":false},{"id":1252422,"name":"Louisa Bhengu","orcid":null,"position":3,"is_corresponding":false},{"id":717204,"name":"Thirona Naicker","orcid":"0000-0001-7146-7159","position":4,"is_corresponding":false},{"id":1252423,"name":"Lindsay Lambie","orcid":null,"position":5,"is_corresponding":false},{"id":1252036,"name":"Liani Smit","orcid":"0000-0002-4502-7405","position":6,"is_corresponding":false},{"id":917425,"name":"Karen Fieggen","orcid":"0000-0002-2910-6306","position":7,"is_corresponding":false},{"id":1252037,"name":"Anneline Lochan","orcid":"0000-0002-7351-9693","position":8,"is_corresponding":false},{"id":1252038,"name":"Jessica Dawson","orcid":"0000-0002-8773-4634","position":9,"is_corresponding":false},{"id":741852,"name":"Phelelani Thokozani Mpangase","orcid":"0000-0001-8280-8940","position":10,"is_corresponding":false},{"id":1252039,"name":"Marc Hauptfleisch","orcid":"0000-0002-3654-7038","position":11,"is_corresponding":false},{"id":1252424,"name":"Gail Scher","orcid":null,"position":12,"is_corresponding":false},{"id":1252425,"name":"Odirile Tabane","orcid":null,"position":13,"is_corresponding":false},{"id":1252426,"name":"Marelize Immelman","orcid":null,"position":14,"is_corresponding":false},{"id":1252040,"name":"Michael Urban","orcid":"0000-0002-9392-0206","position":15,"is_corresponding":false},{"id":735004,"name":"Amanda Krause","orcid":"0000-0002-7157-0807","position":16,"is_corresponding":false},{"id":1252034,"name":"Fahmida Essop","orcid":"0000-0003-3738-002X","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:00:57.233748Z","pmid":"38824262","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":[]}