Biallelic variants in the RFC4 gene cause a rapidly progressive congenital myopathy with severe hypotonia and axial weakness

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F25%3A10497820" target="_blank" >RIV/00064203:_____/25:10497820 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/25:10497820

Výsledek na webu

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

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.nmd.2025.105366" target="_blank" >10.1016/j.nmd.2025.105366</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Biallelic variants in the RFC4 gene cause a rapidly progressive congenital myopathy with severe hypotonia and axial weakness

Popis výsledku v původním jazyce

The RFC4 gene has recently been linked to a multisystemic disorder Morimoto-Ryu-Malicdan neuromuscular syndrome, with myopathy being one of the key symptoms described in nine patients. We report the case of two brothers with a rapidly progressive congenital myopathy characterized by severe hypotonia and axial muscle weakness associated with previously unpublished biallelic variants in the RFC4 gene. Whole exome sequencing revealed biallelic variants NM_002916.5:c.1019_1020insCAAA and NM_002916.5:c.982_983insACT, corresponding to the protein-level changes p.(Gly341Lysfs*4) and p.(Thr328delinsAsnSer) in both brothers. This case expands the phenotypic spectrum of Morimoto-Ryu-Malicdan neuromuscular syndrome, highlighting severe early-onset axial muscle weakness, severe hypotonia, and preserved intellectual development. We also provide novel insights into the clinical progression and potential multidisciplinary interventions for patients with Morimoto-Ryu-Malicdan neuromuscular syndrome. Our findings highlight the importance of advanced genetic diagnostics and international collaboration in identifying rare neuromuscular diseases and improving the clinical management of affected patients.

Název v anglickém jazyce

Biallelic variants in the RFC4 gene cause a rapidly progressive congenital myopathy with severe hypotonia and axial weakness

Popis výsledku anglicky

The RFC4 gene has recently been linked to a multisystemic disorder Morimoto-Ryu-Malicdan neuromuscular syndrome, with myopathy being one of the key symptoms described in nine patients. We report the case of two brothers with a rapidly progressive congenital myopathy characterized by severe hypotonia and axial muscle weakness associated with previously unpublished biallelic variants in the RFC4 gene. Whole exome sequencing revealed biallelic variants NM_002916.5:c.1019_1020insCAAA and NM_002916.5:c.982_983insACT, corresponding to the protein-level changes p.(Gly341Lysfs*4) and p.(Thr328delinsAsnSer) in both brothers. This case expands the phenotypic spectrum of Morimoto-Ryu-Malicdan neuromuscular syndrome, highlighting severe early-onset axial muscle weakness, severe hypotonia, and preserved intellectual development. We also provide novel insights into the clinical progression and potential multidisciplinary interventions for patients with Morimoto-Ryu-Malicdan neuromuscular syndrome. Our findings highlight the importance of advanced genetic diagnostics and international collaboration in identifying rare neuromuscular diseases and improving the clinical management of affected patients.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/NW24-04-00349" target="_blank" >NW24-04-00349: Multiomický přístup v kombinaci se systematickým sbíráním dat pro objasňování patomechanizmů u dědičné senzitivní neuropatie</a><br>

Návaznosti

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

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Neuromuscular Disorders

ISSN

0960-8966

e-ISSN

1873-2364

Svazek periodika

51

Číslo periodika v rámci svazku

June

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

5

Strana od-do

105366

Kód UT WoS článku

001487376100001

EID výsledku v databázi Scopus

2-s2.0-105004073798