Biallelic variants identified in 36 Pakistani families and trios with autism spectrum disorder
Rattachement africain : pk, ca, gb. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
With its high rate of consanguineous marriages and diverse ethnic population, little is currently understood about the genetic architecture of autism spectrum disorder (ASD) in Pakistan. Pakistan has a highly ethnically diverse population, yet with a high proportion of endogamous marriages, and is therefore anticipated to be enriched for biallelic disease-relate variants. Here, we attempt to determine the underlying genetic abnormalities causing ASD in thirty-six small simplex or multiplex families from Pakistan. Microarray genotyping followed by homozygosity mapping, copy number variation analysis, and whole exome sequencing were used to identify candidate. Given the high levels of consanguineous marriages among these families, autosomal recessively inherited variants were prioritized, however de novo/dominant and X-linked variants were also identified. The selected variants were validated using Sanger sequencing. Here we report the identification of sixteen rare or novel coding variants in fifteen genes (ARAP1, CDKL5, CSMD2, EFCAB12, EIF3H, GML, NEDD4, PDZD4, POLR3G, SLC35A2, TMEM214, TMEM232, TRANK1, TTC19, and ZNF292) in affected members in eight of the families, including ten homozygous variants in four families (nine missense, one loss of function). Three heterozygous de novo mutations were also identified (in ARAP1, CSMD2, and NEDD4), and variants in known X-linked neurodevelopmental disorder genes CDKL5 and SLC35A2. The current study offers information on the genetic variability associated with ASD in Pakistan, and demonstrates a marked enrichment for biallelic variants over that reported in outbreeding populations. This information will be useful for improving approaches for studying ASD in populations where endogamy is commonly practiced.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Biallelic variants identified in 36 Pakistani families and trios with autism spectrum disorder
- Date Crossref
- 22/04/2024
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
International Islamic University Department of Biological Sciences pays non établi dans la noticeUniversité ou école supérieure
-
Centre for Addiction and Mental Health pays non établi dans la noticeÉtablissement de santé
-
University of Toronto Institute of Medical Science pays non établi dans la noticeUniversité ou école supérieure
-
University College London pays non établi dans la noticeUniversité ou école supérieure
-
Molecular Neuropsychiatry and Development (MiND) Lab pays non établi dans la noticeStructure de recherche
-
Department of Psychiatry pays non établi dans la noticeInstitution
Department of Biological Sciences — International Islamic University, Centre for Addiction and Mental Health et Institute of Medical Science — University of Toronto, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.