Gene-Targeted Analysis of Clinically Diagnosed Long QT Russian Families

Abstract

SummaryLong QT syndrome (LQTS) has great genetic heterogeneity: more than 500 mutations have been described in several genes. Despite many advances, a genetic diagnosis still cannot be established in 25-30% of patients. The aim of the present study was to perform genetic evaluation in 9 Russian families with LQTS; here we report the results of 4 positive probands and their relatives (a total of 16 individuals). All subjects underwent clinical examination, 12-lead ECG, and Holter monitoring. Genetic analysis of the 14 genes mainly involved in LQTS was performed using a next-generation sequencing approach. We identified two new mutations (KCNQ1 gene) and 6 known mutations (AKAP9, ANK2, KCNE1 and KCNJ2 genes) in 4 out of 9 probands, some of which have already been described in association with LQTS. Segregation studies suggest a possible causative role for KCNQ1 p.(Leu342Pro), AKAP9 p.(Arg1609Lys), KCNE1 p.(Asp85Asn), and KCNJ2 p.(Arg82Gln) variations. Our study confirmed the high genetic heterogeneity of this disease and highlights the difficulties to reveal clear pathogenic genotypes also in large pedigrees. To the best of our knowledge, this is the first genetic study of LQTS patients from Russian families. (Int Heart J 2017; 58: 81-87)

Endurance Exercise Ability in the Horse: A Trait with Complex Polygenic Determinism

“…However, its putative regulatory functions in exercise-related pathways in the horse must now be extensively investigated. Mutations in KCNQ1 have been identified in human patients with severe ventricular arrhythmia, a long QT interval and slow ventricular repolarization on the ECG signal (Wu et al, 2016; Maltese et al, 2017). If the lncRNA were to modulate the expression of the KNCQ1 gene (and perhaps other genes) by hybridization and the induction of conformational changes in the chromatin, cardiac excitability might be affected.…”

Early impairment of the full‐field photopic negative response in patients with Stargardt disease and pathogenic variants of the ABCA4 gene

“…All patients had typical clinical phenotype with either localized or diffuse yellow flecks and/or various degrees of macular atrophy at fundus examination. All patients presented pathogenic or likely pathogenic variants in the ABCA4 gene confirmed by next generation sequencing technology . Exclusion criteria included myopia greater than six dioptres, amblyopia, corneal opacities, cataract, history of previous ocular trauma or surgery, other maculopathies than Stargardt macular dystrophy, glaucoma and any other ocular or neurological disorder likely to affect retinal function.…”

“…In‐solution target enrichment (‘Nextera Rapid Capture Enrichment’) on Illumina platform was performed to sequencing all coding exons and flanking exon/intron boundaries of the ABCA4 gene known to be associated with Stargardt macular dystrophy. The raw read data in fastq format were analysed to generate the list of sequence variants using an in‐house pipeline, as previously described …”

Persistent QT Prolongation in a Child with Gitelman Syndrome and <i>SCN5A</i> H558R Polymorphism

“…SLC12A3 A588V mutation and SCN5A H558R polymorphism were identified. No other mutations of LQTS 1-13 genes, which have already been confirmed to be pathogenic, 6,7) or reported variants that relate to the QT interval, were identified.…”