Mutation Spectrum of the Gene Kcnq1 in Russian Patients With Long Qt Syndrome

Поляк, М Е; Ivanova, Elena; Поляков, А. В.; Заклязьминская, Е. В.

doi:10.15829/1560-4071-2016-10-15-20

Cited by 2 publications

(1 citation statement)

References 5 publications

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“…With three harboring participants, the frequency in the Ivanovo population equals 8.9 × 10 −4 with lower and upper 95% confidence interval (CI) margins 2.0 × 10 −4 and 2.6 × 10 −3 , respectively. The Thr96Arg substitution, however, was classified by VarSome as VUS, had no supporting evidence for pathogenicity in ClinVar, and was not observed among the variants discovered in 9 and 53 unrelated Russian families with the long QT syndrome (Polyak et al, 2016;Maltese et al, 2017). The presence of this variant in the general Russian population without any prevalence in patients may suggest that its pathogenicity needs to be confirmed by future independent submissions.…”

Section: Overrepresented Known Pathogenic and Likely Pathogenic Variantsmentioning

confidence: 91%

Targeted Sequencing of 242 Clinically Important Genes in the Russian Population From the Ivanovo Region

et al. 2021

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We performed a targeted sequencing of 242 clinically important genes mostly associated with cardiovascular diseases in a representative population sample of 1,658 individuals from the Ivanovo region northeast of Moscow. Approximately 11% of 11,876 detected variants were not found in the Single Nucleotide Polymorphism Database (dbSNP) or reported earlier in the Russian population. Most novel variants were singletons and doubletons in our sample, and virtually no novel alleles presumably specific for the Russian population were able to reach the frequencies above 0.1–0.2%. The overwhelming majority (99.3%) of variants detected in this study in three or more copies were shared with other populations. We found two dominant and seven recessive known pathogenic variants with allele frequencies significantly increased compared to those in the gnomAD non-Finnish Europeans. Of the 242 targeted genes, 28 were in the list of 59 genes for which the American College of Medical Genetics and Genomics (ACMG) recommended the reporting of incidental findings. Based on the number of variants detected in the sequenced subset of ACMG59 genes, we approximated the prevalence of known pathogenic and novel or rare protein-truncating variants in the complete set of ACMG59 genes in the Ivanovo population at 1.4 and 2.8%, respectively. We analyzed the available clinical data and observed the incomplete penetrance of known pathogenic variants in the 28 ACMG59 genes: only 1 individual out of 12 with such variants had the phenotype most likely related to the variant. When known pathogenic and novel or rare protein-truncating variants were considered together, the overall rate of confirmed phenotypes was about 19%, with maximum in the subset of novel protein-truncating variants. We report three novel protein truncating variants in APOB and one in MYH7 observed in individuals with hypobetalipoproteinemia and hypertrophic cardiomyopathy, respectively. Our results provide a valuable reference for the clinical interpretation of gene sequencing in Russian and other populations.

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Section: Overrepresented Known Pathogenic and Likely Pathogenic Variantsmentioning

confidence: 91%

Targeted Sequencing of 242 Clinically Important Genes in the Russian Population From the Ivanovo Region

et al. 2021

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Molecular genetic basis of sudden cardiac death in the young with cardiomyopathy of various origins

et al. 2019

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Приведен обзор современной литературы, посвященной проблеме судебно-медицинской интерпретации результатов молекулярно-генетического исследования внезапно умерших лиц молодого возраста. Авторы попытались провести параллель между морфологическими маркерами различных вариантов кардиомиопатии как наиболее часто встречающегося заболевания при внезапной смерти в молодом возрасте и ассоциации с генетическими мутациями в генах, ответственных за синтез белков саркомера, десмосом и мембранных каналов. По результатам анализа предложены направления дальнейших исследований для повышения точности судебно-медицинского диагноза в случаях смерти лиц молодого возраста. Ключевые слова: внезапная сердечная смерть, кардиомиопатия, гены-кандидаты наследственной предрасположенности.

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Mutation Spectrum of the Gene Kcnq1 in Russian Patients With Long Qt Syndrome

Cited by 2 publications

References 5 publications

Targeted Sequencing of 242 Clinically Important Genes in the Russian Population From the Ivanovo Region

Targeted Sequencing of 242 Clinically Important Genes in the Russian Population From the Ivanovo Region

Molecular genetic basis of sudden cardiac death in the young with cardiomyopathy of various origins

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