Mutations in NEBL encoding the cardiac Z-disk protein nebulette are associated with various cardiomyopathies

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F16%3A10323794" target="_blank" >RIV/00064203:_____/16:10323794 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/16:10323794

Result on the web

<a href="http://dx.doi.org/10.5114/aoms.2016.59250" target="_blank" >http://dx.doi.org/10.5114/aoms.2016.59250</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.5114/aoms.2016.59250" target="_blank" >10.5114/aoms.2016.59250</a>

Result language

angličtina

Original language name

Mutations in NEBL encoding the cardiac Z-disk protein nebulette are associated with various cardiomyopathies

Original language description

Introduction: Transgenic mice overexpressing mutated NEBL, encoding the cardiac-specific Z-disk protein nebulette, develop severe cardiac phenotypes. Since cardiomyopathies are commonly familial and because mutations in a single gene may result in variable phenotypes, we tested the hypothesis that NEBL mutations are associated with cardiomyopathy. Material and methods: We analyzed 389 patients, including cohorts of patients with dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), and left ventricular non-compaction cardiomyopathy (LVNC). The 28 coding exons of the NEBL gene were sequenced. Further bioinformatic analysis was used to distinguish variants. Results: In total, we identified six very rare heterozygous missense mutations in NEBL in 7 different patients (frequency 1.8%) in highly conserved codons. The mutations were not detectable in 320 Caucasian sex-matched unrelated individuals without cardiomyopathy and 192 Caucasian sex-matched blood donors without heart disease. Known cardiomyopathy genes were excluded in these patients. The mutations p.H171R and p.1652L were found in 2 HCM patients. Further, p.Q581R and p.S747L were detected in 2 DCM patients, while the mutation p.A175T was identified independently in two unrelated patients with DCM. One LVNC patient carried the mutation p.P916L. All HCM and DCM related mutations were located in the nebulin-like repeats, domains responsible for actin binding. Interestingly, the mutation associated with LVNC was located in the C-terminal serine-rich linker region. Conclusions: Our data suggest that NEBL mutations may cause various cardiomyopathies. We herein describe the first NEBL mutations in HCM and LVNC. Our findings underline the notion that the cardiomyopathies are true allelic diseases.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FA - Cardiovascular diseases including cardio-surgery

OECD FORD branch

—

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

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

Name of the periodical

Archives of Medical Science

ISSN

1734-1922

e-ISSN

—

Volume of the periodical

12

Issue of the periodical within the volume

2

Country of publishing house

PL - POLAND

Number of pages

16

Pages from-to

263-278

UT code for WoS article

000374510200004

EID of the result in the Scopus database

2-s2.0-84963722188