title: Exome sequencing reveals SPG11 mutations causing juvenile ALS.
abstract: We report here the description of a nonconsanguineous family with 2 affected individuals with a recessively inherited juvenile motor neuron disease. Exome sequencing of these 2 affected individuals led us to identify 2 compound heterozygous deletions leading to a frameshift and a premature stop codon in the SPG11 gene. One of these deletions, c.5199delA in exon 30, has not been previously reported. Interestingly, these deletions are associated with an intrafamilial phenotypic heterogeneity as one affected has atypical juvenile amyotrophic lateral sclerosis (ALS) and the other has classical hereditary spastic paraplegia with thin corpus callosum. Our findings confirm SPG11 as a genetic cause of juvenile amyotrophic lateral sclerosis and indicate that SPG11 mutations could be associated with 2 different clinical phenotypes within the same family.
authors.affiliation: Centre of Excellence in Neuroscience of Université de Montréal, CHUM Research Center and the Department of Medicine, Montreal, Quebec, Canada.
authors.forename: Hussein
authors.initials: H
authors.lastname: Daoud
authors.forename: Sirui
authors.initials: S
authors.lastname: Zhou
authors.forename: Anne
authors.initials: A
authors.lastname: Noreau
authors.forename: Mike
authors.initials: M
authors.lastname: Sabbagh
authors.forename: Veronique
authors.initials: V
authors.lastname: Belzil
authors.forename: Alexandre
authors.initials: A
authors.lastname: Dionne-Laporte
authors.forename: Christine
authors.initials: C
authors.lastname: Tranchant
authors.forename: Patrick
authors.initials: P
authors.lastname: Dion
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D011506:Proteins / Q000235:genetics*
chemical_list: D011506:Proteins; C520412:SPG11 protein, human