%0 Journal Article
%T SYNE1-ataxia: Novel genotypic and phenotypic findings.
%A Indelicato E
%A Nachbauer W
%A Fauth C
%A Krabichler B
%A Schossig A
%A Eigentler A
%A Dichtl W
%A Wenning G
%A Wagner M
%A Fanciulli A
%A Janecke A
%A Boesch S
%J Parkinsonism Relat Disord
%V 62
%N 0
%D 05 2019
%M 30573412
%F 4.402
%R 10.1016/j.parkreldis.2018.12.007
%X 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.<BR>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.<BR>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.<BR>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.