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
The pancreas consists of exocrine and endocrine compartments. In the exocrine pancreas, cystic fibrosis transmembrane conductance regulator (CFTR) functions mainly in ductal epithelial cells as a chloride and bicarbonate channel. Its activity depends on proper protein folding, trafficking, and localization to the apical membrane. This systematic narrative review aims to synthesize the available evidence on the role of protein sorting machinery in CFTR channelopathies and its contribution to exocrine pancreatic dysfunction. A thorough search was conducted using PRISMA criteria on PubMed, Wiley Online Library, and Scopus for studies published in English between January 2000 and November 2025. Twenty studies that met the inclusion criteria were included in this review. Pathogenic CFTR variants impair protein folding, endoplasmic reticulum (ER) exit, and endosomal recycling, resulting in reduced apical membrane expression and stability. These defects disrupt the localization of associated transporters and secretory proteins, impair ductal bicarbonate secretion, alter zymogen handling, and promote acinar injury, although these claims are supported mainly by indirect experimental models and therefore require clinical confirmation. CFTR channelopathies in the exocrine pancreas encompass both ion transport defects and broader disruptions of protein sorting machinery. CFTR may contribute to the assembly, stabilization, or localization of selected apical transport complexes, and its loss can secondarily alter epithelial organization. Therapeutic approaches targeting both channel correction and intracellular trafficking may improve pancreatic function and mitigate disease progression.
Aime Patrick Niyomugabo, Leopold Ntakirutimana, A. Alagbonsi· Channels· 0 citations
Aims: Current diabetes mellitus (DM) prevention and treatment strategies rely on risk factors adapted from developed countries, which may not be effective in most poor sub-Saharan Africa settings. This study investigated the association between diabetic treatment outcomes and complications with sociodemographic and diabetic risk factors among type 2 DM (T2DM) patients in Rwanda. Methods: This cross-sectional study analyzed the records of T2DM patients who accessed care at Kigali University Teaching Hospital (CHUK) between January and December 2020, using a non-random sampling technique. Treatment outcomes (improved or not improved based on glycemic control target) and complication outcomes (presence or absence of DM-related microvascular and macrovascular events) were the primary outcome variables. Data were analyzed using t -tests, chi-square tests, and multivariable analyses as appropriate. Results: After adjusting for confounders, only age remained significantly associated with treatment and complication outcomes. The adjusted prevalence ratio (PR) of treatment outcomes for patients aged <50 years was 1.43 (95% CI 1.07–1.92; p = 0.016) and for those aged 50–64 years was 1.12 (95% CI 0.83–1.52; p = 0.462), both relative to the ≥65 years reference category. The adjusted PR for complication outcomes was 0.59 (95% CI 0.40–0.86; p = 0.005) for patients aged <50 years and 0.72 (95% CI 0.57–0.91; p = 0.007) for those aged 50–64 years, compared with the ≥65 years reference category. The adjusted PRs for smoking, alcohol consumption, pharmacological therapy, non-pharmacological therapy, and diet were attenuated and no longer statistically significant (all p > 0.05). Conclusion: The outcomes of diabetic treatment in Rwanda are associated with the age of the patients, rather than the type of therapy or the assessed sociodemographic and risk factors. The causal interpretation and generalizability of this study are limited by its cross-sectional design, non-random sampling, and the single-center setting.
A. Alagbonsi, Aime P. N. Kagina, Denyse Ingabire et al.· Diabetes, Metabolic Syndrome...· 0 citations
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