Autosomal dominant congenital non-progressive ataxia overlaps with the SCA15 locus
Autosomal dominant congenital non-progressive ataxia overlaps with the SCA15 locus
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DOI：
10.1212/01.wnl.0000147299.80872.d1
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发表时间：
2004-12-28
期刊：
影响因子：
9.9
通讯作者：
Richards, RI
中科院分区：
文献类型：
--
作者：
Dudding, TE;Friend, K;Richards, RI
背景：大多数单纯非进行性先天性小脑性共济失调的患者具有散发性，遗传和病因不明。几个小家族已经报道了显性遗传性非进行性先天性共济失调（NPCA）。方法：作者确定了一个常染色体显性型先天性非进行性小脑性共济失调伴认知障碍的四代家系，并对其进行了临床鉴定。在排除了几个SCA定位（SCA-1、2、3、4、5、6、7、8、10、12、17、IOSCA和DRPLA）后，进行了全基因组连锁研究。结果：家庭检查显示，所有受影响的成员都有步态失调和认知障碍，影像学表现为构音障碍、韵律障碍、运动障碍、眼球震颤、张力障碍运动和小脑发育不全。没有锥体束功能障碍和感觉改变的临床征象。在该家族的全基因组搜索中发现了与染色体3p的连锁，D3S3630位点的最大两点负载评分为4.26。根据重组事件的定义，这种定位到pter的位置远低于D3S1304。这与SCA15位点重叠，微卫星标记D3S1304和D3S1620之间的关键重叠区域（约8 cM）。结论：常染色体显性先天性非进行性小脑共济失调伴或不伴小脑发育不全与3pter染色体上的SCA15位点重叠。
Background: Most patients with pure nonprogressive congenital cerebellar ataxia have a sporadic form of unknown heredity and etiology. Several small families have been reported with a dominantly inherited nonprogressive congenital ataxia ( NPCA). Methods: The authors ascertained and clinically characterized a four-generation pedigree segregating an autosomal dominant type of congenital nonprogressive cerebellar ataxia associated with cognitive impairment. Following the exclusion of several SCA localizations (SCA-1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 17, IOSCA, and DRPLA), a genome-wide linkage study was performed. Results: Examination of the family showed that all affected members had gait ataxia and cognitive disability with variable features of dysarthria, dysmetria, dysdiadochokinesia, nystagmus, dystonic movements, and cerebellar hypoplasia on imaging. Clinical signs of pyramidal tract dysfunction and sensory changes were absent. A genome-wide search in this family detected linkage to chromosome 3p with a maximum two-point lod score of 4.26 at D3S3630. This localization to the pter is distal to D3S1304, as defined by a recombination event. This overlaps with the SCA15 locus, with the critical overlapping region between the microsatellite markers, D3S1304 and D3S1620 (approximately 8 cM). Conclusion: Autosomal dominant congenital nonprogressive cerebellar ataxia with or without cerebellar hypoplasia overlaps with the SCA15 locus on chromosome 3pter.