Spinocerebellar ataxia type 15 (SCA15) maps to 3p24.2-3pter:: exclusion of the ITPR1 gene, the human orthologue of an ataxic mouse mutant
Spinocerebellar ataxia type 15 (SCA15) maps to 3p24.2-3pter:: exclusion of the ITPR1 gene, the human orthologue of an ataxic mouse mutant
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DOI：
10.1016/s0969-9961(03)00029-9
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发表时间：
2003-07-01
影响因子：
6.1
通讯作者：
Forrest, SM
中科院分区：
文献类型：
--
作者：
Knight, MA;Kennerson, ML;Forrest, SM
我们研究了一个大型的澳大利亚家族显性遗传纯小脑共济失调，SCA 15。该疾病的特征是在一些家族成员中进展速度非常缓慢，并且主要是上级蚓部萎缩，并且小脑半球萎缩程度较小。重复扩增检测未发现CAG/CTG或ATTCT/AGAAT重复扩增与该家系疾病分离。全基因组扫描显示了与3号染色体短臂连锁的重要证据。使用D3 S3706获得了最高的两点LOD评分（Z = 3.4，θ = 0.0）。单倍型分析鉴定了将SCA 15位点置于两侧为标记D3 S3630和D3 S1304的11.6 cM区域内的重组体。小鼠同线区包含两个共济失调突变体itpr 1（-/-）和opt，影响肌醇1，4，5-三磷酸1型受体ITPR 1基因。ITPR 1主要表达于小脑浦肯野细胞中。从两个代表性的受影响的家庭成员的突变分析排除了ITPR 1基因的编码区参与SCA 15的发病机制。因此，itpr 1（-/-）和opt ITPR 1小鼠突变体，其各自导致共济失调，与人SCA 15基因座不是等位基因。(C)2003 Elsevier Science（美国）。All rights reserved.
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.