Molecular analysis confirmed common ancestor of 10 Czech families with long QT syndrome carrying C926T-KCNQ1 variant

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F19%3A00072095" target="_blank" >RIV/65269705:_____/19:00072095 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/19:00108568

Výsledek na webu

<a href="https://www.nature.com/articles/s41431-019-0494-2" target="_blank" >https://www.nature.com/articles/s41431-019-0494-2</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Molecular analysis confirmed common ancestor of 10 Czech families with long QT syndrome carrying C926T-KCNQ1 variant

Popis výsledku v původním jazyce

Introduction: Long QT syndrome (LQTS) is a hereditary arrhythmic syndrome characterized by abnormal prolongation of QT interval, increased risk of ventricular arrhythmias, and sudden death. It is the most often diagnosed hereditary arrhythmic disorder with prevalence 1:2000. The KCNQ1 gene is one of the 3 major genes (KCNQ1, KCNH2 and SCN5A) which account for 75 % of the genetically identified LQTS cases. The same KCNQ1 mutation c.926C&gt;T (p.T309I) was identified in 10 putatively unrelated families. Materials and Methods: 11 highly polymorphic short tandem repeats (STR) markers were chosen for haplotype analysis in 10 families. Multiplex PCR and fragment analysis were performed to identify variant linked to the mutation across families. Single nucleotide polymorphism (SNP) analysis was performed with HumanKaryomap-12 DNA Analysis Kit (Illumina) in one member of each family. 6219 SNPs on p arm of chromosome 11 were analysed. Results: The same haplotype was identified in the nearest region of the mutation spot in every family by STR analysis and then confirmed by SNP analysis, which also identified possible crossing-overs. The maximum size of the area shared by all families is 658407 bp and contains the whole sequence of KCNQ1 gene. The maximum size of the area shared by two families is 12633501 bp. Conclusion: Allelic frequencies of identified alleles in STR markers in control population suggest that there is only one common ancestor with mutation c.926C&gt;T in the group of families investigated in this study.

Název v anglickém jazyce

Molecular analysis confirmed common ancestor of 10 Czech families with long QT syndrome carrying C926T-KCNQ1 variant

Popis výsledku anglicky

Introduction: Long QT syndrome (LQTS) is a hereditary arrhythmic syndrome characterized by abnormal prolongation of QT interval, increased risk of ventricular arrhythmias, and sudden death. It is the most often diagnosed hereditary arrhythmic disorder with prevalence 1:2000. The KCNQ1 gene is one of the 3 major genes (KCNQ1, KCNH2 and SCN5A) which account for 75 % of the genetically identified LQTS cases. The same KCNQ1 mutation c.926C&gt;T (p.T309I) was identified in 10 putatively unrelated families. Materials and Methods: 11 highly polymorphic short tandem repeats (STR) markers were chosen for haplotype analysis in 10 families. Multiplex PCR and fragment analysis were performed to identify variant linked to the mutation across families. Single nucleotide polymorphism (SNP) analysis was performed with HumanKaryomap-12 DNA Analysis Kit (Illumina) in one member of each family. 6219 SNPs on p arm of chromosome 11 were analysed. Results: The same haplotype was identified in the nearest region of the mutation spot in every family by STR analysis and then confirmed by SNP analysis, which also identified possible crossing-overs. The maximum size of the area shared by all families is 658407 bp and contains the whole sequence of KCNQ1 gene. The maximum size of the area shared by two families is 12633501 bp. Conclusion: Allelic frequencies of identified alleles in STR markers in control population suggest that there is only one common ancestor with mutation c.926C&gt;T in the group of families investigated in this study.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/NV16-30571A" target="_blank" >NV16-30571A: Klinický význam a elektrofyziologické zhodnocení mutace c.926C>T genu KCNQ1 (p.T309I) jako možné „founder mutation“ syndromu dlouhého intervalu QT</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů