From targeted SCN1A analysis to whole exome sequencing: clinical utility and novel genetic findings in a Hungarian paediatric epilepsy cohort

Whole-exome sequencing in pediatric drug-resistant epilepsy: diagnostic yield and clinical impact in a resource-limited setting

Rare genetic variation in adults with surgically treated temporal lobe epilepsy: An exome sequencing study

The results suggest that single‐gene causes are rare in adults with TLE, consistent with previous reports indicating a low diagnostic yield of presurgical genetic testing and further support a predominantly polygenic architecture of TLE.

Systematic reanalysis of next-generation sequencing data in 101 neuromuscular disorder families enhances diagnostic yield, reveals intronic variants, and identifies a novel disease gene

Genetic landscape of pediatric seizures in Southeast China: identification of a novel GLI3 frameshift variant through whole-exome sequencing

Pediatric seizure disorders are clinically and genetically heterogeneous. Whole-exome sequencing has improved the detection of rare genetic variants in childhood epilepsy; however, data from pediatric populations in Southeast China remain limited. This study aimed to characterize the genetic landscape of pediatric seizure disorders in Southeast China and to evaluate the clinical diagnostic yield of whole-exome sequencing. This retrospective observational study included 21 pediatric patients with seizure disorders who were recruited at the Fifth Hospital of Xiamen, Fujian, China, between January 2021 and June 2024. Clinical data were extracted from medical records. Whole-exome sequencing was performed on DNA extracted from peripheral blood. Sequence variants were annotated, filtered, and classified according to the guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Copy-number variants were evaluated using exome-based algorithms. Descriptive statistics were used because of the limited sample size. WES identified three clinically relevant, likely pathogenic findings in 3 of 21 patients, corresponding to a provisional diagnostic yield of 14.3%. The remaining 62 of 65 variants were of uncertain significance (VUS). The three retained variants included a GLI3 frameshift variant (exon 2: c.90_91insCAGATGTGAGC; p.Glu31Glnfs*3) and two copy-number variants (16p13.12-16p13.11 duplication and Xp22.31 deletion) with established clinical significance. Functional analysis of all 65 variants revealed that ion channel genes and neurodevelopmental genes were the most frequently affected categories. Whole-exome sequencing identified clinically relevant genetic findings in a subset of Southeast Chinese children with seizure disorders. The novel GLI3 frameshift variant may suggest an expansion of the GLI3-associated phenotypic spectrum, but further segregation, functional validation, and larger cohort studies are needed. The high proportion of variants of uncertain significance highlights the ongoing challenges of genetic interpretation in pediatric seizure disorders.

Whole-exome sequencing identifies rare genetic variants in Egyptian patients with hypertrophic cardiomyopathy: a pilot study.

As the first genetic study of hypertrophic cardiomyopathy in an Egyptian population, this work expands the global mutational spectrum, demonstrates the utility of genetic testing for risk stratification and personalised management, and underscores the need to diversify genomic datasets for equitable precision medicine.

Whole exome sequencing of an Algerian Parkinson’s disease cohort: an exploratory study identifying rare variants in putative candidate genes

Parkinson’s disease (PD), a complex neurodegenerative disorder, is increasingly prevalent, with a strong genetic component. While environmental factors contribute, the exact cause remains elusive. Understanding PD’s genetic basis is vital for advancing research and treatment. This study seeks to investigate the genetic diversity of Parkinson’s disease in the Algerian population using whole exome sequencing (WES), with the goal of identifying rare variants across genes potentially associated with the disease. Whole exome sequencing (WES) was performed on a cohort of 19 Algerian patients with clinically confirmed Parkinson’s disease, including 8 patients with a positive family history. Variant annotation and functional effect prediction were performed using SnpEff, in conjunction with multiple reference genomic databases. Variant calling results were stored in Variant Call Format (VCF). Variants were classified according to their minor allele frequency (MAF): rare variants were defined as those with a MAF between 0.1% and 1%, while novel variants were defined as those with a MAF ≤ 0.1% or absent from all queried reference databases. Whole exome sequencing analysis identified 73 variants distributed across 22 genes in 19 Algerian patients with Parkinson’s disease. Following prioritization, nine variants were detected across six candidate genes (DDOST, AUP1, SNORD66, TRPM7, ORC6, and GLUD2), whose association with Parkinson’s disease had not been previously reported in North African populations. These genes are involved in several cellular functions, including protein homeostasis, DNA repair, cellular metabolism, and oxidative stress response. Among them, GLUD2 emerges as a particularly compelling candidate requiring functional validation for future investigations. This preliminary study highlights the genetic diversity of Parkinson’s disease in the Algerian population and underscores the value of whole exome sequencing for the identification of rare variants in underrepresented populations. The findings suggest potential novel research avenues that may contribute to expanding knowledge of the genetic architecture of the disease. Replication studies and functional validation will be required to confirm the biological and clinical relevance of the identified variants.