title: Sequencing analysis of the ITPR1 gene in a pure autosomal dominant spinocerebellar ataxia series.
abstract: Spinocerebellar ataxia type 15 and 16 (SCA15/16) are autosomal dominant cerebellar ataxias that are slowly progressive with a predominantly pure ataxia phenotype (ADCA III). The locus for SCA15 was first mapped to 3p24.2-3pter and subsequently full or partial deletions in the inositol 1,4,5-triphosphate receptor type 1 (ITPR1) gene were identified in several ADCA III families that segregated with the disease. A single missense coding variant has been described, but the pathogenicity of this change has not been proven. We sequenced the entire coding region and flanking regions of ITPR1 in unrelated ADCA III families (n = 38) that were negative for large deletions on whole genome arrays, and for which SCAs 1, 2, 3, 6, 7, 8, 11, 12, 14, 17 and the Friedreich's ataxia expansion were excluded in all probands. Mutation at SCA5, 10, and 27 was also excluded in some families. A number of coding and noncoding polymorphisms were identified but no ITPR1 mutations were found. The results indicate that point mutations in ITPR1 are at best a rare cause of ADCA III.
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Joyce
authors.initials: J
authors.lastname: van de Leemput
authors.forename: Fabienne
authors.initials: F
authors.lastname: Wavrant-De Vrièze
authors.forename: Ian
authors.initials: I
authors.lastname: Rafferty
authors.forename: Jose M
authors.initials: JM
authors.lastname: Bras
authors.forename: Paola
authors.initials: P
authors.lastname: Giunti
authors.forename: Elizabeth M C
authors.initials: EM
authors.lastname: Fisher
authors.forename: John A
authors.initials: JA
authors.lastname: Hardy
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
authors.forename: Henry
authors.initials: H
authors.lastname: Houlden
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*; D020754:Spinocerebellar Ataxias / Q000145:classification / Q000235:genetics*; D055815:Young Adult
chemical_list: C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors