Genomic insights from a deeply phenotyped highly consanguineous neurodevelopmental disorders cohort.

Autor:	Akter H; Genetics and Genomic Medicine Centre (GGMC), NeuroGen Healthcare, Dhaka, Bangladesh; Laboratory of Population Genetics, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh., Rahaman MA; Genetics and Genomic Medicine Centre (GGMC), NeuroGen Healthcare, Dhaka, Bangladesh., Eshaque TB; Genetics and Genomic Medicine Centre (GGMC), NeuroGen Healthcare, Dhaka, Bangladesh., Mohamed N; Center for Applied and Translational Genomics, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health, Dubai, UAE., Islam A; Genetics and Genomic Medicine Centre (GGMC), NeuroGen Healthcare, Dhaka, Bangladesh; GenomeArc Inc., Mississauga, ON, Canada., Morshed M; Genetics and Genomic Medicine Centre (GGMC), NeuroGen Healthcare, Dhaka, Bangladesh., Shahin Z; Imperial College London, London, United Kingdom., Muhaimin A; Genetics and Genomic Medicine Centre (GGMC), NeuroGen Healthcare, Dhaka, Bangladesh., Foyzullah AM; Genetics and Genomic Medicine Centre (GGMC), NeuroGen Healthcare, Dhaka, Bangladesh., Mim RA; Genetics and Genomic Medicine Centre (GGMC), NeuroGen Healthcare, Dhaka, Bangladesh., Omar FB; Genetics and Genomic Medicine Centre (GGMC), NeuroGen Healthcare, Dhaka, Bangladesh., Hasan MN; Genetics and Genomic Medicine Centre (GGMC), NeuroGen Healthcare, Dhaka, Bangladesh; GenomeArc Inc., Mississauga, ON, Canada., Satsangi D; College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE., Ahmed N; Genetics and Genomic Medicine Centre (GGMC), NeuroGen Healthcare, Dhaka, Bangladesh., Al Saba A; Laboratory of Population Genetics, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh., Jahan N; Centre for Precision Therapeutics (NPT), NeuroGen Healthcare, Dhaka, Bangladesh., Hossen MA; Centre for Precision Therapeutics (NPT), NeuroGen Healthcare, Dhaka, Bangladesh., Mondol MA; Centre for Precision Therapeutics (NPT), NeuroGen Healthcare, Dhaka, Bangladesh., Sakib AS; Centre for Precision Therapeutics (NPT), NeuroGen Healthcare, Dhaka, Bangladesh., Kabir R; Centre for Precision Therapeutics (NPT), NeuroGen Healthcare, Dhaka, Bangladesh., Jahan Chowdhury MS; Centre for Precision Therapeutics (NPT), NeuroGen Healthcare, Dhaka, Bangladesh., Shams N; Centre for Precision Therapeutics (NPT), NeuroGen Healthcare, Dhaka, Bangladesh., Afroz S; Bangladesh Shishu Hospital and Institute, Dhaka, Bangladesh., Kanta SI; Bangladesh Shishu Hospital and Institute, Dhaka, Bangladesh., Bhuiyan SJ; Pediatric neurology. Evercare Hospital, Dhaka, Bangladesh., Biswas R; Bangladesh Shishu Hospital and Institute, Dhaka, Bangladesh., Hanif S; Center for Applied and Translational Genomics, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health, Dubai, UAE., Tambi R; Center for Applied and Translational Genomics, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health, Dubai, UAE., Nassir N; Center for Applied and Translational Genomics, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health, Dubai, UAE; College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE., Rahman MM; Department of Paediatric Neurology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh., Duan J; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark; Department of Biomedicine and the iSEQ Centre, Aarhus University, Aarhus, Denmark; Center for Genomics and Personalized Medicine, Aarhus, Denmark., D Børglum A; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark; Department of Biomedicine and the iSEQ Centre, Aarhus University, Aarhus, Denmark; Center for Genomics and Personalized Medicine, Aarhus, Denmark., Amin R; Ministry of Health and Family Welfare, Government of People Republic of Bangladesh, Dhaka, Bangaldesh., Basiruzzaman M; Centre for Precision Therapeutics (NPT), NeuroGen Healthcare, Dhaka, Bangladesh., Kamruzzaman M; Bangladesh Shishu Hospital and Institute, Dhaka, Bangladesh., Sarker S; Centre for Precision Therapeutics (NPT), NeuroGen Healthcare, Dhaka, Bangladesh; Bangladesh Shishu Hospital and Institute, Dhaka, Bangladesh., Woodbury-Smith M; Biosciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., Uddin KMF; Genetics and Genomic Medicine Centre (GGMC), NeuroGen Healthcare, Dhaka, Bangladesh; Department of Biochemistry, Holy Family Red Crescent Medical College, Dhaka, Bangladesh., Nabi AHMN; Laboratory of Population Genetics, Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka, Bangladesh., Uddin M; Center for Applied and Translational Genomics, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health, Dubai, UAE; GenomeArc Inc., Mississauga, ON, Canada; College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE. Electronic address: dafil.mohammed@genomearc.com.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2024 Sep 26; Vol. 27 (1), pp. 101282. Date of Electronic Publication: 2024 Sep 26.
DOI:	10.1016/j.gim.2024.101282
Abstrakt:	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. Competing Interests: Conflict of Interest Corresponding author, Mohammed Uddin owns share of GenomeArc. All other authors declare no conflicts of interest. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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