ABSTRACT Introduction Autism spectrum disorder (ASD) is a neurodevelopmental condition with substantial genetic and phenotypic heterogeneity. However, populations of African ancestry remain underrepresented in genomic studies, limiting understanding of ASD genetic architecture. This study aimed to characterize rare, clinically relevant genetic variants in a Rwandan pediatric ASD cohort using trio‐based whole‐exome sequencing (WES). Methods Trio‐based WES was performed in 31 Rwandan pediatric patients with ASD (aged 2–18 years) and their parents. Variants were analyzed using a trio‐based workflow and classified according to American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines. Results Eleven candidate variants were identified in 9 of 31 patients, including four likely pathogenic variants and seven variants of uncertain significance. This resulted in a diagnostic yield of 12.9% (4/31), expanded to 29.0% when phenotypically concordant variants of uncertain significance were considered. Most likely pathogenic variants were identified in individuals with syndromic ASD who presented with intellectual disability, epilepsy, and global developmental delay. Likely pathogenic findings included two single nucleotide variants in GABRB3, SYNGAP1, and two copy‐number variants involving the GNAS locus and chromosome 1p35.3‐p35.2. Conclusions The diagnostic yield observed in this cohort is consistent with previous trio‐based WES studies of ASD. The findings support the clinical utility of WES for the genetic evaluation of ASD and underscore the need for expanded genomic studies in African populations.
Olivier Hakizimana, J. Hitayezu, J. P. Uyisenga et al.· Molecular Genetics & Genomic...· 0 citations
INTRODUCTION: CSS (CSS) is a rare neurodevelopmental disorder characterized by developmental delay, intellectual disability, hypotonia, distinctive craniofacial dysmorphism, and hypoplasia or aplasia of the distal phalanges or nails, particularly of the fifth digits. Pathogenic variants involving genes encoding components of the Switch/Sucrose Non-Fermentable chromatin-remodeling complex especially ARID1B gene critical for embryonic development and gene regulation represent the most common molecular cause of the syndrome. Although advances in genomic technologies have improved recognition of CSS worldwide over the past 3 decades, reports from sub-Saharan Africa remain limited.
CASE PRESENTATION: We report a male patient referred to Rwanda Military Teaching Hospital, Pediatric Department in Medical genetic unit for global developmental delay and feeding difficulties. Clinical examination revealed, hypotonia, developmental milestone delay, coarse facial appearance, sparse scalp hair, thick eyebrows, long eyelashes, broad nasal bridge, anteverted nostrils, low-set ears, micrognathia, and hypoplastic toenails.
Results: Conventional cytogenetic analysis demonstrated a male karyotype (46, XY). Whole exome sequencing-based copy number variants analysis identified a 7.3 Mb interstitial deletion involving chromosome 6q25.3–q25.1 encompassing the ARID1B gene. The finding was confirmed by multiplex ligation-dependent probe amplification, establishing the diagnosis of CSS type 1. The patient was managed in multidisciplinary team approach including physiotherapy and speech therapy and he demonstrated clinical improvement.
CONCLUSION: This report describes the first genetically confirmed case of CSS in Rwanda. It highlights the diagnostic utility of advanced molecular genetic testing in children with developmental delay and dysmorphic features and underscores the importance of expanding access to clinical genetic services in resource-limited settings to reduce diagnostic odyssey and timely patient management.
Adelaide Urugwiro Horanimpundu, Norbert Dukuze, Hannah Umutoni Mugaragu et al.· Rwanda medical journal· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
