title: Sporadic infantile-onset spinocerebellar ataxia caused by missense mutations of the inositol 1,4,5-triphosphate receptor type 1 gene.
abstract: Mutations in the inositol 1,4,5-triphosphate receptor type 1 gene (ITPR1) have been identified in families with early-onset spinocerebellar ataxia type 29 (SCA29) and late-onset SCA15, but have not been found in sporadic infantile-onset cerebellar ataxia. We examined if mutations of ITPR1 are also involved in sporadic infantile-onset SCA. Sixty patients with childhood-onset cerebellar atrophy of unknown etiology and their families were examined by whole-exome sequencing. We found de novo heterozygous ITPR1 missense mutations in four unrelated patients with sporadic infantile-onset, nonprogressive cerebellar ataxia. Patients displayed nystagmus, tremor, and hypotonia from very early infancy. Nonprogressive ataxia, motor delay, and mild cognitive deficits were common clinical findings. Brain magnetic resonance imaging revealed slowly progressive cerebellar atrophy. ITPR1 missense mutations cause infantile-onset cerebellar ataxia. ITPR1-related SCA includes sporadic infantile-onset cerebellar ataxia as well as SCA15 and SCA29.
authors: Department of Child Neurology, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo, 187-8551, Japan, masasaki@ncnp.go.jp.
authors: Masayuki
authors: M
authors: Sasaki
authors: Chihiro
authors: C
authors: Ohba
authors: Mizue
authors: M
authors: Iai
authors: Shinichi
authors: S
authors: Hirabayashi
authors: Hitoshi
authors: H
authors: Osaka
authors: Takuya
authors: T
authors: Hiraide
authors: Hirotomo
authors: H
authors: Saitsu
authors: Naomichi
authors: N
authors: Matsumoto
mesh_terms: D001921:Brain / Q000473:pathology; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology
chemical_list: C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors