Titre : | SYNE1-ataxia: Novel genotypic and phenotypic findings |
Revue : | Parkinsonism & related disorders |
Auteurs : | Indelicato E, Auteur ; Nachbauer W ; Fauth C ; Krabichler B ; Schossig A ; Eigentler A ; Dichtl W ; Wenning G ; Wagner M ; Fanciulli A ; Janecke A ; Boesch S |
Type de document : | Article |
Editeur : | England, 11/12/2018 |
Langues: | Anglais |
Résumé : |
INTRODUCTION: SYNE1 encodes nesprin-1, a scaffold protein which is involved in the binding between cytoskeleton, nuclear envelope and other subcellular compartments. In 2007, recessive truncating SYNE1 mutations have been linked to a genetic form of pure cerebellar ataxia with adult onset and mild phenotype. Subsequent reports described a number of patients with SYNE1-ataxia and widespread neurological involvement including features of motor neuron disease. Recently, heterozygote missense SYNE1 mutations have been associated with muscular disorders, such as Emery-Dreifuss muscular dystrophy, arthrogryposis multiplex congenita and dilated cardiomyopathy.
METHODS: Herein we describe novel genotypic and phenotypic findings in an independent cohort of 5 patients with SYNE1-ataxia referring to the Department of Neurology of the Innsbruck Medical University and performed a review of the related literature. RESULTS: We report 3 novel mutations and describe for the first time myocardial involvement in a patient with a complicated spastic-ataxic phenotype and C-terminal mutation. In the literature, mutations associated with additional motor neuron signs spanned over the entire gene, but patients with a particularly severe phenotype and premature death bore C-terminal mutations. CONCLUSION: Our findings support a genotype-phenotype correlation in SYNE1-ataxia and suggest the need for a systematic cardiologic evaluation in the setting of complicated spastic-ataxia phenotypes. |
Pubmed / DOI : | DOI : 10.1016/j.parkreldis.2018.12.007 / Pubmed : 30573412 |
N° Profil MNM : | 2018122 |
En ligne : | http://www.ncbi.nlm.nih.gov/pubmed/30573412 |