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Lookup NU author(s): Dr Marc Woodbury-Smith
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The Authors. Purpose: The genetic underpinning of neurodevelopmental disorders (NDDs) in diverse ethnic populations, especially those with high rates of consanguinity, remains largely unexplored. Here, we aim to elucidate genomic insight from 576 well-phenotyped and highly consanguineous (16%) NDD cohort. Methods: We used chromosomal microarray (CMA; N:247), exome sequencing (ES; N:127), combined CMA and ES (N:202), and long-read genome sequencing to identify genetic etiology. Deep clinical multivariate data were coupled with genomic variants for stratification analysis. Results: Genetic diagnosis rates were 17% with CMA, 29.92% with ES, and 37.13% with combined CMA and ES. Notably, children of consanguineous parents showed a significantly higher diagnostic yield (P < .01) compared to those from nonconsanguineous parents. Among the ES-identified pathogenic variants, 36.19% (38/105) were novel, implicating 35 unique genes. Long-read sequencing of seizure participants unresolved by combined test identified expanded FMR1 trinucleotide repeats. Additionally, we identified 2 recurrent X-linked variants in the G6PD in 3.65% (12/329) of NDD participants. These variants were absent in large-population control cohorts and cohort comprising neurodevelopmental and neuropsychiatric populations of European descendants, indicating a possible associated risk factor potentially resulting from ancient genetic drift. Conclusion: This study unveils unique clinical and genomic insights from a consanguinity rich Bangladeshi NDD cohort, highlighting a strong association of G6PD with NDD in this population.
Author(s): Akter H, Rahaman MA, Eshaque TB, Mohamed N, Islam A, Morshed M, Shahin Z, Muhaimin A, Foyzullah AM, Mim RA, Omar FB, Hasan MN, Satsangi D, Ahmed N, Al Saba A, Jahan N, Hossen MA, Mondol MA, Sakib AS, Kabir R, Jahan Chowdhury MS, Shams N, Afroz S, Kanta SI, Bhuiyan SJ, Biswas R, Hanif S, Tambi R, Nassir N, Rahman MM, Duan J, D Borglum A, Amin R, Basiruzzaman M, Kamruzzaman M, Sarker S, Woodbury-Smith M, Uddin KMF, Nabi AHMN, Uddin M
Publication type: Article
Publication status: Published
Journal: Genetics in Medicine
Year: 2025
Volume: 27
Issue: 1
Print publication date: 01/01/2025
Online publication date: 26/09/2024
Acceptance date: 19/09/2024
Date deposited: 21/11/2024
ISSN (print): 1098-3600
ISSN (electronic): 1530-0366
Publisher: Elsevier BV
URL: https://doi.org/10.1016/j.gim.2024.101282
DOI: 10.1016/j.gim.2024.101282
Data Access Statement: All variants of clinical interest are available in supplemental tables. Moreover, the variants of clinical interest have also been submitted in ClinVar database (SUB14023450). More detailed information is available from the corresponding authors upon request.
PubMed id: 39342494
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