👤 Selim Colak

Congenital heart diseases (CHDs) are complex traits that manifest in diverse clinical phenotypes such as the Tetralogy of Fallot (TOF), valvular and ventricular/atrial septal defects. Genetic mechanisms of CHDs have remained largely unclear to date. Copy number variations (CNVs) have been implicated in many complex diseases but their impact has not been examined extensively in various forms of CHD lesions. We report in this study, to the best of our knowledge, the largest cohort of Saudi Arab CHD patients to date who were evaluated using genome-wide CNV analysis. In a sample of 134 Saudi Arab patients with CHD, 66 exhibited pathogenic or likely pathogenic CNVs. Notably, 21 copy number gains and 11 copy number losses were detected that encompassed 141 genes and 146 genes, respectively. The most frequent gains were on 17q21.31, 8p11.21, and 22q11.23, whereas the losses were primarily localized to 16p11.2. Interestingly, all lesions have had gains at 17q21.31. Septal defects had also gains at 8p11.21 and 22q11.23, valvular lesions at 8p11.21, 22q11.23, and 2q13, and TOF at 16p11.2. Functional and network analyses demonstrated that cardiovascular and nervous system development and function as well as cell death/survival were most significantly associated with CNVs, thus highlighting the potentially important genes likely to be involved in CHD, including Show less

Voltage-gated potassium channels are highly diverse proteins representing the most complex class of voltage-gated ion channels from structural and functional perspectives. Deficiency of these channels usually results in various human disorders. To describe a novel autosomal recessive syndrome associated with We used SNP arrays, linkage analyses, autozygosity mapping, whole-exome sequencing, RT-PCR and two-electrode voltage-clamp recording. We identified a missense variant (p.Arg89Gln) in Show less