Case report: Dihydropyridine receptor ( CACNA1S ) congenital myopathy, a novel phenotype with early onset periodic paralysis

related congenital myopathy is an emerging recently described entity. In this report we describe 2 sisters with mutations in the gene and the novel phenotype of congenital myopathy and infantile onset episodic weakness. Both sisters had neonatal onset hypotonia, muscle weakness, and delayed walking....

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Bibliographic Details
Published in:Frontiers in neurology 2024-02, Vol.15, p.1359479
Main Authors: Aburahma, Samah K, Rousan, Liqa A, Shboul, Mohammad, Biella, Fabio, Lucchiari, Sabrina, Comi, Giacomo Pietro, Meola, Giovanni, Pagliarani, Serena
Format: Article
Language:English
Subjects:
CACNA1S
Cav1.1
congenital myopathy
DHPR
episodic weakness
Neurology
splice minigene assay
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Summary:related congenital myopathy is an emerging recently described entity. In this report we describe 2 sisters with mutations in the gene and the novel phenotype of congenital myopathy and infantile onset episodic weakness. Both sisters had neonatal onset hypotonia, muscle weakness, and delayed walking. Episodic weakness started in infancy and continued thereafter, provoked mostly by cold exposure. Muscle imaging revealed fat replacement of gluteus maximus muscles. Next generation sequencing found the missense p.Cys944Tyr variant and the novel splicing variant c.3526-2A>G in . Minigene assay revealed the splicing variant caused skipping of exon 28 from the transcript, potentially affecting protein folding and/or voltage dependent activation. This novel phenotype supports the notion that there are age related differences in the clinical expression of gene mutations. This expands our understanding of mutations located in regions of the outside the highly conserved S4 segment, where most mutations thus far have been identified.
ISSN:1664-2295
1664-2295
DOI:10.3389/fneur.2024.1359479