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.
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Authors | Masayuki Sasaki, Chihiro Ohba, Mizue Iai, Shinichi Hirabayashi, Hitoshi Osaka, Takuya Hiraide, Hirotomo Saitsu, Naomichi Matsumoto |
Journal | Journal of neurology
(J Neurol)
Vol. 262
Issue 5
Pg. 1278-84
(May 2015)
ISSN: 1432-1459 [Electronic] Germany |
PMID | 25794864
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ITPR1 protein, human
- Inositol 1,4,5-Trisphosphate Receptors
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Topics |
- Brain
(pathology)
- Child
- DNA Mutational Analysis
- Female
- Genetic Predisposition to Disease
(genetics)
- Humans
- Inositol 1,4,5-Trisphosphate Receptors
(genetics)
- Magnetic Resonance Imaging
- Male
- Mutation, Missense
(genetics)
- Spinocerebellar Ataxias
(genetics, pathology)
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