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

Result code in 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>
Alternative codes found
RIV/00216208:11130/25:10497820
Result on the web
<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>

Result language
angličtina
Original language name
Biallelic variants in the RFC4 gene cause a rapidly progressive congenital myopathy with severe hypotonia and axial weakness
Original language description
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progressive congenital myopathy characterized by severe hypotonia and axial muscle weakness associated with previously unpublished biallelic variants in the RFC4 gene.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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30103 - Neurosciences (including psychophysiology)

Project
<a href="/en/project/NW24-04-00349" target="_blank" >NW24-04-00349: Addressing unmet needs in rare diseases: natural history study and multi-omics analysis in hereditary sensory neuropathies</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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