No abstract

Congenital heart disease (CHD) is one of the most common forms of birth defects worldwide, with a prevalence of 1–2% in newborns. CHD is a multifactorial disease partially caused by genetic defects, including chromosomal abnormalities and single gene mutations. Here, we describe the Sidra Cardiac Registry, which includes 52 families and a total of 178 individuals, and investigate the genetic etiology of CHD in Qatar. We reviewed the results of genetic tests conducted in patients as part of their clinical evaluation, including chromosomal testing. We also performed whole exome sequencing (WES) to identify potential causative variants. Sixteen patients with CHD had chromosomal abnormalities that explained their complex CHD phenotype, including six patients with trisomy 21. Moreover, using exome analysis, we identified potential CHD variants in 24 patients, revealing 65 potential variants in 56 genes. Four variants were classified as pathogenic/likely pathogenic based on the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) classification; these variants were detected in four patients. This study sheds light on several potential genetic variants contributing to the development of CHD. Additional functional studies are needed to better understand the role of the identified variants in the pathogenesis of CHD.

No abstract

Epilepsy is one of the most common neurological disorders. The cost to the health system and the impact on quality of life for patients with intractable epilepsies and associated comorbidities is significant. Disease etiology and pathogenesis are still not well understood. Genetic mutations have been shown to be associated with 70% of epilepsies, with the majority being non-monogenic, and the remaining 30% enigmatic. This knowledge gap necessitates further research. The goal of this study is to partially bridge this gap through the genetic analysis of a cohort of patients with epilepsy from an understudied and highly consanguineous population, primarily of ethnicities from the Middle East and North Africa region. Whole exome sequencing was carried out in 81 patients with epilepsy and their family members at a tertiary center in Qatar. We used the data to identify pathogenic variants and type HLA alleles for 13 class I & II genes. We associated the resulting alleles with disease status, using controls of a closely related ethnicity. The genetic yield was approximately 22% for known epilepsy genes. We also suggest a list of 20 genes that could be culprits. Analysis of the biological pathways in which these genes are involved show that focal and generalized epilepsy genes are highly interwound. HLA analysis revealed that class II HLA genes are associated with disease status, particularly DRB4*03:01N, which plays a strong protective role. Our findings suggest that an immune etiology may contribute to the disease together with a genetic culprit, emphasizing the complexity of the etiology of the disease.