Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

Major intra-familial phenotypic heterogeneity and incomplete penetrance due to a CACNA1A pathogenic variant

Abstract : The CACNA1A gene encodes a calcium-dependent voltage channel, localized in neuronal cells. Pathogenic variants in this gene are known to lead to a broad clinical spectrum including episodic ataxia type 2, spinocerebellar ataxia type 6, familial hemiplegic migraine, and more recently epileptic encephalopathy. We report a large family revealing a wide variability of neurological manifestations associated with a CACNA1A missense pathogenic variant. The index case had early-onset epileptic encephalopathy with progressive cerebellar atrophy, although his mother and his great-grandmother suffered from paroxystic episodic ataxia. His grandfather and great grand-aunt reported no symptoms, but two of her sons displayed early-onset ataxia with intellectual disability. Two of her little daughters suffered from gait disorders, and also from epilepsy for one of them. All these relatives were carriers of the previously described heterozygous variant in CACNA1A gene. We report here the first family leading to major clinical variability and incomplete penetrance. Our family highlights the difficulties to provide accurate genetic counselling concerning prenatal diagnosis regarding highly variable severity of the clinical presentation.
Type de document :
Article dans une revue
Liste complète des métadonnées
Contributeur : Accord Elsevier CCSD Connectez-vous pour contacter le contributeur
Soumis le : lundi 25 octobre 2021 - 10:23:59
Dernière modification le : jeudi 1 septembre 2022 - 03:58:41
Archivage à long terme le : : mercredi 26 janvier 2022 - 18:56:14


Fichiers produits par l'(les) auteur(s)


Distributed under a Creative Commons Paternité - Pas d'utilisation commerciale 4.0 International License



Chloé Angelini, Julien van Gils, Antoine Bigourdan, Pierre-Simon Jouk, Didier Lacombe, et al.. Major intra-familial phenotypic heterogeneity and incomplete penetrance due to a CACNA1A pathogenic variant. European Journal of Medical Genetics, Elsevier, In press, ⟨10.1016/j.ejmg.2018.08.011⟩. ⟨hal-01952641⟩



Consultations de la notice


Téléchargements de fichiers