Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) due to CAG repeat expansion in the CACNA1A gene on chromosome 19p
Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) due to CAG repeat expansion in the CACNA1A gene on chromosome 19p
复制标题
DOI：
10.1093/hmg/6.11.1973
复制
发表时间：
1997-10-01
影响因子：
3.5
通讯作者：
Frontali, M
中科院分区：
文献类型：
--
作者：
Jodice, C;Mantuano, E;Frontali, M
编码α（1A）电压依赖性钙通道亚基的CACNA 1A基因的点突变是家族性偏瘫性偏头痛（FHM）和发作性共济失调2型（EA 2）的原因。此外，在患有进行性脊髓小脑共济失调（称为SCAG）的患者中发现了在基因的3'端的CAG重复基序的扩增，其小于导致动态突变障碍的那些。在本工作中，分析了具有CACNA 1A基因的小CAG扩增的两个新家族，在一个家族中，临床诊断为EA 2，CAG（23）重复等位基因在表现出不同发作间期症状的患者中分离，从仅眼球震颤到严重的进行性小脑共济失调，未发现与CAG扩增不平衡的编码和内含子-外显子连接序列的额外突变。在第二个家族中，最初被分类为未知类型的常染色体显性小脑共济失调，代间等位基因大小变化显示CAG（20）等位基因与EA 2表型相关，CAG（25）等位基因与进行性小脑共济失调相关。这些结果显示EA 2和SCAG是具有高表型变异性的相同疾病，至少部分与重复数相关，并提示小扩增可能不像以前报道的那样稳定，还提供了CACNA 1A基因的编码序列和内含子-外显子连接序列的改进。
Point mutations of the CACNA1A gene coding for the alpha(1A) voltage-dependent calcium channel subunit are responsible for familial hemiplegic migraine (FHM) and episodic ataxia type 2 (EA2). In addition, expansions of the CAG repeat motif at the 3' end of the gene, smaller than those responsible for dynamic mutation disorders, were found in patients with a progressive spinocerebellar ataxia, named SCAG, In the present work, the analysis of two new families with small CAG expansions of the CACNA1A gene is presented, in one family, with a clinical diagnosis of EA2, a CAG(23) repeat allele segregated in patients showing different interictal symptoms, ranging from nystagmus only to severe progressive cerebellar ataxia, No additional mutations in coding and intron-exon junction sequences in disequilibrium with the CAG expansion were found, In the second family, initially classified as autosomal dominant cerebellar ataxia of unknown type, an inter-generational allele size change showed that a CAG(20) allele was associated with an EA2 phenotype and a CAG(25) allele with progressive cerebellar ataxia, These results show that EA2 and SCAG are the same disorder with a high phenotypic variability, at least partly related to the number of repeats, and suggest that the small expansions may not be as stable as previously reported, A refinement of the coding and intron-exon junction sequences of the CACNA1A gene is also provided.