Clinical utility of FLNC variants identified in 4 young Czech people with sudden cardiac arrest for clinical management of their at risk relatives

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F19%3A10396190" target="_blank" >RIV/00216208:11130/19:10396190 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Clinical utility of FLNC variants identified in 4 young Czech people with sudden cardiac arrest for clinical management of their at risk relatives

Popis výsledku v původním jazyce

Introduction: Mutations in FLNC gene were initially related to muscular dystrophy and myofibrillar myopathy but more recently, variants in FLNC were reported to cause familial cardiomyopathies in the absence of skeletal muscle defects. Truncating mutations in FLNC cause an overlapping phenotype of dilated cardiomyopathy or arrhythmogenic cardiomyopathy while missense mutations are associated with familiar hypertrophic cardiomyopathy and might also play an important role in cases of unexplained sudden cardiac death (SCD) in young subjects. Materials and Methods: We investigated the cohort of Czech cardiac arrest (CA) survivors/victims by performing massively parallel sequencing using a custom-made panel comprising 229 cardiac conditions-related genes (NimbleGen/Illumina). Detected variants were validated by Sanger sequencing, including their familial segregation and classified according to ACMG. Results: We have identified variants in FLNC gene in 3 cases. In 2/3 cases the rare variant NM_001458.4 (FLNC):c.102G&gt;A p.(Trp34*) was found in non-related Czech subjects (26 years old male CA victim and 16 years old female CA survivor). NM_001458.4 (FLNC):c.1732G&gt;T p.(Gly578Cys) in CA victim, where this variant was coexistent with probable causative variant in TTN gene. Conclusion: Both, truncating and missense mutations in the FLNC gene might be associated with SCA and demonstrate the clinical utility of genetic testing in at-risk family members. The aim of our study is to increase the usage of genetic analysis in post mortem investigations of SCD in the young cases in order to improve clinical management of relatives at risk in the Czech Republic.

Název v anglickém jazyce

Clinical utility of FLNC variants identified in 4 young Czech people with sudden cardiac arrest for clinical management of their at risk relatives

Popis výsledku anglicky

Introduction: Mutations in FLNC gene were initially related to muscular dystrophy and myofibrillar myopathy but more recently, variants in FLNC were reported to cause familial cardiomyopathies in the absence of skeletal muscle defects. Truncating mutations in FLNC cause an overlapping phenotype of dilated cardiomyopathy or arrhythmogenic cardiomyopathy while missense mutations are associated with familiar hypertrophic cardiomyopathy and might also play an important role in cases of unexplained sudden cardiac death (SCD) in young subjects. Materials and Methods: We investigated the cohort of Czech cardiac arrest (CA) survivors/victims by performing massively parallel sequencing using a custom-made panel comprising 229 cardiac conditions-related genes (NimbleGen/Illumina). Detected variants were validated by Sanger sequencing, including their familial segregation and classified according to ACMG. Results: We have identified variants in FLNC gene in 3 cases. In 2/3 cases the rare variant NM_001458.4 (FLNC):c.102G&gt;A p.(Trp34*) was found in non-related Czech subjects (26 years old male CA victim and 16 years old female CA survivor). NM_001458.4 (FLNC):c.1732G&gt;T p.(Gly578Cys) in CA victim, where this variant was coexistent with probable causative variant in TTN gene. Conclusion: Both, truncating and missense mutations in the FLNC gene might be associated with SCA and demonstrate the clinical utility of genetic testing in at-risk family members. The aim of our study is to increase the usage of genetic analysis in post mortem investigations of SCD in the young cases in order to improve clinical management of relatives at risk in the Czech Republic.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10600 - Biological sciences

Projekt

<a href="/cs/project/NV18-02-00237" target="_blank" >NV18-02-00237: Diagnostika příčin náhlé srdeční smrti u lidí ve věku 0-35 let pomocí molekulárně-genetických metod – pilotní studie</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