title: Identification of a novel Twinkle mutation in a family with infantile onset spinocerebellar ataxia by whole exome sequencing.
abstract: Whole exome sequencing combined with homozygosity mapping comprises a genetic diagnostic tool to identify genetic defects in families with multiple affected members, compatible with presumed autosomal recessively inherited neurometabolic/neurogenetic disease. These tools were applied to a family with two individuals manifesting ataxia, associated with peripheral sensory neuropathy, athetosis, seizures, deafness, and ophthalmoplegia. A novel homozygous missense mutation c.1366C>G (L456V) in C10orf2 (the Twinkle gene) was identified, confirming infantile onset spinocerebellar ataxia in the probands. Signs in infantile onset spinocerebellar ataxia follow a fairly distinct pattern, affecting early development, followed by ataxia and loss of skills. However, this very rare disease was previously reported only in Finland. We suggest that infantile onset spinocerebellar ataxia should be more frequently considered in the differential diagnosis of neurometabolic diseases in childhood. Next-generation sequencing and its use along with homozygosity mapping offer highly promising techniques for molecular diagnosis, especially in small families affected with very rare neurometabolic disorders such as infantile onset spinocerebellar ataxia.
authors.affiliation: Metabolism Unit, Department of Pediatrics, Faculty of Medicine, Hacettepe University, Sıhhiye, Ankara, Turkey.
authors.forename: Halil
authors.initials: H
authors.lastname: Dündar
authors.forename: Rıza Köksal
authors.initials: RK
authors.lastname: Ozgül
authors.forename: Dilek
authors.initials: D
authors.lastname: Yalnızoğlu
authors.forename: Sevim
authors.initials: S
authors.lastname: Erdem
authors.forename: Kader Karlı
authors.initials: KK
authors.lastname: Oğuz
authors.forename: Deniz
authors.initials: D
authors.lastname: Tuncel
authors.forename: Cağrı Mesut
authors.initials: CM
authors.lastname: Temuçin
authors.forename: Ali
authors.initials: A
authors.lastname: Dursun
mesh_terms: D017668:Age of Onset; D004265:DNA Helicases / Q000235:genetics*; D059472:Exome; D005260:Female; D006801:Humans; D008297:Male; D024101:Mitochondrial Proteins; D009154:Mutation; D010375:Pedigree; D020754:Spinocerebellar Ataxias / Q000235:genetics*
chemical_list: D024101:Mitochondrial Proteins; D004265:DNA Helicases; C431576:TWNK protein, human