| Autor: |
Essop, Fahmida, Dillon, Bronwyn, Mhlongo, Felicity, Bhengu, Louisa, Naicker, Thirona, Lambie, Lindsay, Smit, Liani, Fieggen, Karen, Lochan, Anneline, Dawson, Jessica, Mpangase, Phelelani, Hauptfleisch, Marc, Scher, Gail, Tabane, Odirile, Immelman, Marelize, Urban, Michael, Krause, Amanda |
| Zdroj: |
European Journal of Human Genetics: EJHG; 20240101, Issue: Preprints p1-10, 10p |
| Abstrakt: |
STAC3disorder, or Native American myopathy, is characterised by congenital myopathy, hypotonia, musculoskeletal and palatal anomalies, and susceptibility to malignant hyperthermia. A STAC3c.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 STAC3c.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 STAC3c.851 G > C. The frequencies of various phenotypic characteristics were calculated. In total, 25/127 (20%) laboratory-based samples were homozygous for STAC3c.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 STAC3was 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 STAC3disorder 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 STAC3c.851 G > C variant has an African origin which may be due to an ancient mutation with migration and population bottlenecks. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Full text from SpringerLink