Intragenic TTN Deletions in a Single Family with Dilated Cardiomyopathy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F27283933%3A_____%2F25%3AN0000017" target="_blank" >RIV/27283933:_____/25:N0000017 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064203:_____/25:10504542 RIV/00023001:_____/25:00086166 RIV/00216208:11130/25:10504542

Výsledek na webu

<a href="https://www.dovepress.com/article/download/107962" target="_blank" >https://www.dovepress.com/article/download/107962</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2147/TACG.S550190" target="_blank" >10.2147/TACG.S550190</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Intragenic TTN Deletions in a Single Family with Dilated Cardiomyopathy

Popis výsledku v původním jazyce

The TTN gene (MIM:188840) encodes titin, the largest human protein with exclusive expression in the cardiac and skeletal muscles. Rare variants disrupting the TTN gene are frequent causes of dilated cardiomyopathy and several forms of skeletal myopathy. We report a unique occurrence of two novel, distinct but overlapping intragenic TTN deletions in multiple relatives from a single Czech family with the clinical manifestation of dilated cardiomyopathy (DCM). After clinical exome sequencing using the custom virtual gene panel, two distinct deletions affecting the TTN gene (NM_001267550.2) were detected. The first deletion (3.599 kb in length) encompasses five exons with the breakpoints in exons 326 and 330. The longer one (4.859 kb in length) disrupts exon 326 only. Both deletions segregate with the cardiomyopathy phenotype, and none of the tested individuals carry both. The familial segregation of two distinct intragenic TTN deletions extends the broad spectrum of rare variants in the pathogenesis of DCM. The presence of severely affected carriers of the reported DNA variants and obligatory healthy non-carriers raises the debate on their ancestral origin. Our data demonstrate the clinical benefits of the family cascade screening and molecular genetic analysis in familial DCM, enabling early and effective multidisciplinary medical care.

Název v anglickém jazyce

Intragenic TTN Deletions in a Single Family with Dilated Cardiomyopathy

Popis výsledku anglicky

The TTN gene (MIM:188840) encodes titin, the largest human protein with exclusive expression in the cardiac and skeletal muscles. Rare variants disrupting the TTN gene are frequent causes of dilated cardiomyopathy and several forms of skeletal myopathy. We report a unique occurrence of two novel, distinct but overlapping intragenic TTN deletions in multiple relatives from a single Czech family with the clinical manifestation of dilated cardiomyopathy (DCM). After clinical exome sequencing using the custom virtual gene panel, two distinct deletions affecting the TTN gene (NM_001267550.2) were detected. The first deletion (3.599 kb in length) encompasses five exons with the breakpoints in exons 326 and 330. The longer one (4.859 kb in length) disrupts exon 326 only. Both deletions segregate with the cardiomyopathy phenotype, and none of the tested individuals carry both. The familial segregation of two distinct intragenic TTN deletions extends the broad spectrum of rare variants in the pathogenesis of DCM. The presence of severely affected carriers of the reported DNA variants and obligatory healthy non-carriers raises the debate on their ancestral origin. Our data demonstrate the clinical benefits of the family cascade screening and molecular genetic analysis in familial DCM, enabling early and effective multidisciplinary medical care.

Druh

J_ost - Ostatní články v recenzovaných periodicích

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

The Application of Clinical Genetics

ISSN

1178-704X

e-ISSN

—

Svazek periodika

18

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

NZ - Nový Zéland

Počet stran výsledku

7

Strana od-do

211-217

Kód UT WoS článku

001596564000001

EID výsledku v databázi Scopus

2-s2.0-105018923711