Genetic and Structural Variations in Czech Patients With Congenital Myopathies

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F25%3A10498865" target="_blank" >RIV/00179906:_____/25:10498865 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/25:00141755 RIV/61988987:17110/25:A2603D25 RIV/00216208:11110/25:10498865 RIV/00216208:11130/25:10498865 a 5 dalších

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=KYicLbH7.1" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=KYicLbH7.1</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/cge.14782" target="_blank" >10.1111/cge.14782</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Genetic and Structural Variations in Czech Patients With Congenital Myopathies

Popis výsledku v původním jazyce

Congenital myopathies (CMs) are a heterogeneous group of genetic muscle disorders characterized by hypotonia and muscle weakness, with pathogenic variants identified in at least 41 genes and inheritance patterns including autosomal dominant (AD), recessive (AR), and X-linked (XL). We present 79 unrelated patients with genetically confirmed CM using next-generation sequencing (NGS). A total of 113 mutant alleles carrying 97 different variants with a presumed pathogenic effect were identified. According to the HGMD database, 54 of these variants have been reported exclusively in the Czech CM population to date. All but five variants were small-scale. Large gene deletions were identified in the MTM1, NEB, and RYR1 genes. Sequencing of breakpoint junctions in the identified NEB and RYR1 deletions provided insights into the upstream mechanisms leading to genomic instability and resulting in structural variations. We present the family with dominant inheritance of the NEB deletion of exons 19-78. We assume that our family represents another reported case of a dominant mutation in the NEB gene. Our results contribute to further knowledge in the field of neuromuscular diseases and mutational mechanisms.

Název v anglickém jazyce

Genetic and Structural Variations in Czech Patients With Congenital Myopathies

Popis výsledku anglicky

Congenital myopathies (CMs) are a heterogeneous group of genetic muscle disorders characterized by hypotonia and muscle weakness, with pathogenic variants identified in at least 41 genes and inheritance patterns including autosomal dominant (AD), recessive (AR), and X-linked (XL). We present 79 unrelated patients with genetically confirmed CM using next-generation sequencing (NGS). A total of 113 mutant alleles carrying 97 different variants with a presumed pathogenic effect were identified. According to the HGMD database, 54 of these variants have been reported exclusively in the Czech CM population to date. All but five variants were small-scale. Large gene deletions were identified in the MTM1, NEB, and RYR1 genes. Sequencing of breakpoint junctions in the identified NEB and RYR1 deletions provided insights into the upstream mechanisms leading to genomic instability and resulting in structural variations. We present the family with dominant inheritance of the NEB deletion of exons 19-78. We assume that our family represents another reported case of a dominant mutation in the NEB gene. Our results contribute to further knowledge in the field of neuromuscular diseases and mutational mechanisms.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30101 - Human genetics

Projekt

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

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Clinical Genetics

ISSN

0009-9163

e-ISSN

1399-0004

Svazek periodika

108

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

DK - Dánské království

Počet stran výsledku

6

Strana od-do

678-683

Kód UT WoS článku

001509967000001

EID výsledku v databázi Scopus

2-s2.0-105008430506