Spinocerebellar ataxia type 15 (SCA15) maps to 3p24.2-3pter:: exclusion of the ITPR1 gene, the human orthologue of an ataxic mouse mutant

被引:47
作者
Knight, MA
Kennerson, ML
Anney, RJ
Matsuura, T
Nicholson, GA
Salimi-Tari, P
Gardner, RJM
Storey, E
Forrest, SM
机构
[1] Walter & Eliza Hall Inst Med Res, Australian Genome Res Facil, Melbourne, Vic, Australia
[2] Monash Univ, Dept Neurosci, Melbourne, Vic, Australia
[3] Royal Childrens Hosp, Genet Hlth Serv Victoria, Melbourne, Vic, Australia
[4] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
[5] Concord Hosp, ANZAC Res Inst, Neurobiol Lab, Sydney, NSW, Australia
[6] Concord Hosp, Mol Med Lab, Sydney, NSW, Australia
[7] Univ Melbourne, Royal Childrens Hosp, Dept Paediat, Melbourne, Vic, Australia
[8] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic, Australia
基金
英国医学研究理事会;
关键词
spinocerebellar ataxia; SCA15; ITPR1;
D O I
10.1016/S0969-9961(03)00029-9
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We have studied a large Australian kindred with a dominantly inherited pure cerebellar ataxia, SCA15. The disease is characterised by a very slow rate of progression in some family members, and atrophy predominantly of the superior vermis, and to a lesser extent the cerebellar hemispheres. Repeat expansion detection failed to identify either a CAG/CTG or ATTCT/AGAAT repeat expansions segregating with the disease in this family. A genome-wide scan revealed significant evidence for linkage to the short arm of chromosome 3. The highest two-point LOD score was obtained with D3S3706 (Z = 3.4, theta = 0.0). Haplotype analysis identified recombinants that placed the SCA15 locus within an 11.6-cM region flanked by the markers D3S3630 and D3S1304. The mouse syntenic region contains two ataxic mutants, itpr1(-/-) and opt, affecting the inositol 1,4,5-triphosphate type 1 receptor, ITPR1 gene. ITPR1 is predominantly expressed in the cerebellar Purkinje cells. Mutation analysis from two representative affected family members excluded the coding region of the ITPR1 gene from being involved in the pathogenesis of SCA 15. Thus, the itpr1(-/-) and opt ITPR1 mouse mutants, which each result in ataxia, are not allelic to the human SCA15 locus. (C) 2003 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:147 / 157
页数:11
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