An ITPR1 gene deletion causes spinocerebellar ataxia 15/16: a genetic, clinical and radiological description.
Mov Disord
; 25(13): 2176-82, 2010 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-20669319
ABSTRACT
The purpose of this study was to characterise a novel family with very slowly progressive pure spinocerebellar ataxia (SCA) caused by a deletion in the inositol 1,4,5-triphosphate receptor 1 (ITPR1) gene on chromosome 3. This is a detailed clinical, genetic, and radiological description of the genotype. Deletions in ITPR1 have been shown to cause SCA15/SCA16 in six families to date. A further Japanese family has been identified with an ITPR1 point mutation. The exact prevalence is as yet unknown, but is probably higher than previously thought. The clinical phenotype of the family is described, and videotaped clinical examinations are presented. Serial brain magnetic resonance imaging studies were carried out on one affected individual, and genetic analysis was performed on several family members. Protein analysis confirmed the ITPR1 deletion. Affected subjects display a remarkably slow, almost pure cerebellar syndrome. Serial magnetic resonance imaging shows moderate cerebellar atrophy with mild inferior parietal and temporal cortical volume loss. Genetic analysis shows a deletion of 346,487 bp in ITPR1 (the second largest ITPR1 deletion reported to date), suggesting SCA15 is due to a loss of ITPR1 function. Western blotting of lymphoblastoid cell line protein confirms reduced ITPR1 protein levels. SCA15 is a slowly or nonprogressive pure cerebellar ataxia, which appears to be caused by a loss of ITPR1 function and a reduction in the translated protein. Patients with nonprogressive or slowly progressive ataxia should be screened for ITPR1 defects.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Eliminación de Gen
/
Ataxias Espinocerebelosas
/
Polimorfismo de Nucleótido Simple
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Receptores de Inositol 1,4,5-Trifosfato
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Adult
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Mov Disord
Asunto de la revista:
NEUROLOGIA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Reino Unido