MEREAUX, Jean-Loup; FIRANESCU, Cristina; COARELLI, Giulia; KVARNUNG, Malin; RODRIGUES, Rita; PEGORARO, Elena; TAZIR, Meriem; TAITHE, Frederic; VALTER, Remi; HUIN, Vincent; LIDSTROM, Kristina; BANNEAU, Guillaume; MORAIS, Sara; PARODI, Livia; COUTELIER, Marie; PAPIN, Melanie; SVENNINGSSON, Per; AZULAY, Jean-Philippe; ALONSO, Isabel; NILSSON, Daniel; BRICE, Alexis; LE GUERN, Eric; PRESS, Rayomand; VAZZA, Giovanni; LOUREIRO, Jose Leal; GOIZET, Cyril; DURR, Alexandra; PAUCAR, Martin; STEVANIN, Giovanni

doi:10.1007/s10048-020-00633-2

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Article de revue

Este ítem está publicado en

neurogenetics. 2021-01-23, vol. 22, n° 1, p. 71-79

Resumen en inglés

Spastic ataxias are rare neurogenetic disorders involving spinocerebellar and pyramidal tracts. Many genes are involved. Among them, CAPN1, when mutated, is responsible for a complex inherited form of spastic paraplegia (SPG76). We report the largest published series of 21 novel patients with nine new CAPN1 disease-causing variants and their clinical characteristics from two European university hospitals (Paris and Stockholm). After a formal clinical examination, causative variants were identified by next-generation sequencing and confirmed by Sanger sequencing. CAPN1 variants are a rare cause (~ 1.4%) of young-adult-onset spastic ataxia; however, together with all published cases, they allowed us to better describe the clinical and genetic spectra of this form. Truncating variants are the most frequent, and missense variants lead to earlier age at onset in favor of an additional deleterious effect. Cerebellar ataxia with cerebellar atrophy, dysarthria and lower limb weakness are often associated with spasticity. We also suggest that cognitive impairment and depression should be assessed specifically in the follow-up of SPG76 cases.< Leer menos

Palabras clave en inglés

CAPN1

Cerebellar ataxia

Neurodegeneration

Spastic ataxia

Spastic paraplegia

URI

https://oskar-bordeaux.fr/handle/20.500.12278/117081

DOI

http://dx.doi.org/10.1007/s10048-020-00633-2

Proyecto europeo

European Union’s Horizon 2020 research and innovation programme

Proyecto ANR

Identification of new causative genes in spinocerebellar degenerations by combination of whole genome scan, next-generation sequencing and biological validation in vitro and in vivo - ANR-13-ISV1-0002
Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences

Centros de investigación

Maladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211

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Increasing involvement of CAPN1 variants in spastic ataxias and phenotype-genotype correlations