{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T04:58:35Z","timestamp":1792299515404,"version":"4.4.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Hum Genet"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>STAC3<\/jats:italic>\n                    disorder, or Native American myopathy, is characterised by congenital myopathy, hypotonia, musculoskeletal and palatal anomalies, and susceptibility to malignant hyperthermia. A\n                    <jats:italic>STAC3<\/jats:italic>\n                    c.851\u2009G\u2009&gt;\u2009C (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\n                    <jats:italic>STAC3<\/jats:italic>\n                    c.851\u2009G\u2009&gt;\u2009C 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\n                    <jats:italic>STAC3<\/jats:italic>\n                    c.851\u2009G\u2009&gt;\u2009C. The frequencies of various phenotypic characteristics were calculated. In total, 25\/127 (20%) laboratory-based samples were homozygous for\n                    <jats:italic>STAC3<\/jats:italic>\n                    c.851\u2009G\u2009&gt;\u2009C. 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\n                    <jats:italic>STAC3<\/jats:italic>\n                    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\n                    <jats:italic>STAC3<\/jats:italic>\n                    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\n                    <jats:italic>STAC3<\/jats:italic>\n                    c.851\u2009G\u2009&gt;\u2009C variant has an African origin which may be due to an\u00a0ancient mutation with migration and population bottlenecks.\n                  <\/jats:p>","DOI":"10.1038\/s41431-024-01644-5","type":"journal-article","created":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T14:01:36Z","timestamp":1717250496000},"page":"14-23","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["STAC3 disorder: a common cause of congenital hypotonia in Southern African patients"],"prefix":"10.1038","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3738-002X","authenticated-orcid":false,"given":"Fahmida","family":"Essop","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7560-7307","authenticated-orcid":false,"given":"Bronwyn","family":"Dillon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicity","family":"Mhlongo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louisa","family":"Bhengu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thirona","family":"Naicker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay","family":"Lambie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liani","family":"Smit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2910-6306","authenticated-orcid":false,"given":"Karen","family":"Fieggen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneline","family":"Lochan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Dawson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8280-8940","authenticated-orcid":false,"given":"Phelelani","family":"Mpangase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Hauptfleisch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail","family":"Scher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odirile","family":"Tabane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marelize","family":"Immelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Urban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7157-0807","authenticated-orcid":false,"given":"Amanda","family":"Krause","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,1]]},"reference":[{"key":"1644_CR1","first-page":"1043","volume":"66","author":"AG Bailey","year":"1987","unstructured":"Bailey AG, Bloch EC. 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Individual consents were obtained at other hospitals for the additional national patients. Consent to access their anonymised data for research purposes was obtained from Professor Zane Lombard, PI DDD-Africa study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Consent for photographs was obtained from participants or parent\/guardian.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}