title: Frequency of rare recessive mutations in unexplained late onset cerebellar ataxia.
abstract: Sporadic late onset cerebellar ataxia is a well-described clinical presentation with a broad differential diagnosis that adult neurologists should be familiar with. However, despite extensive clinical investigations, an acquired cause is identified in only a minority of cases. Thereafter, an underlying genetic basis is often considered, even in those without a family history. Here we apply whole exome sequencing to a cohort of 12 patients with late onset cerebellar ataxia. We show that 33% of 'idiopathic' cases harbor compound heterozygous mutations in known ataxia genes, including genes not included on multi-gene panels, or primarily associated with an ataxic presentation.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, NE1 3BZ, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Keogh
authors.forename: H
authors.initials: H
authors.lastname: Steele
authors.forename: K
authors.initials: K
authors.lastname: Douroudis
authors.forename: A
authors.initials: A
authors.lastname: Pyle
authors.forename: J
authors.initials: J
authors.lastname: Duff
authors.forename: R
authors.initials: R
authors.lastname: Hussain
authors.forename: T
authors.initials: T
authors.lastname: Smertenko
authors.forename: H
authors.initials: H
authors.lastname: Griffin
authors.forename: M
authors.initials: M
authors.lastname: Santibanez-Koref
authors.forename: R
authors.initials: R
authors.lastname: Horvath
authors.forename: P F
authors.initials: PF
authors.lastname: Chinnery
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004739:England; D059472:Exome / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D059645:Mutation Rate; D017422:Sequence Analysis, DNA; D013132:Spinocerebellar Degenerations / Q000235:genetics*