Del-Favero J, Krols L, Michalik A, Theuns J, Löfgren A, Goossens D, Wehnert A, Van den Bossche D, Van Zand K, Backhovens H, van Regenmorter N, Martin J J, Van Broeckhoven C
Laboratory of Neurogenetics, Flanders Interuniversity Institute for Biotechnology, Born-Bunge Foundation, University of Antwerp, B-2610 Antwerpen, Belgium.
Hum Mol Genet. 1998 Feb;7(2):177-86. doi: 10.1093/hmg/7.2.177.
Autosomal dominant cerebellar ataxia with retinal degeneration (ADCAII) was previously mapped by linkage analysis studies to chromosome 3p12-p21.1 (SCA7). Positional cloning efforts have recently identified a novel gene, SCA7 , containing a translated CAG repeat, expanded in SCA7 patients. We cloned the SCA7 gene from a yeast artificial chromosome (YAC) clone contig spanning the SCA7 candidate region. Using a combination of genomic sequencing and cosmid-based exon trapping, two expressed sequence tags were identified. Sequencing of the corresponding cDNA clones and RT-PCR analysis identified the full-length SCA7 cDNA. Together, our sequence data defined the intron/exon boundaries of the first two coding exons of the SCA7 gene, with the first exon containing the expanded CAG repeat. Further, sequence comparison with the published SCA7 cDNA identified one additional putative exon in the 5'-UTR region of the SCA7 gene. The SCA7 gene was mapped on the YAC contig in the 2.5 cM interval between D3S1600 and D3S1287. In one extended Belgian SCA7 pedigree the expanded alleles ranged from 38 to at least 55 repeats with allele lengths being inversely correlated with onset age of ADCAII symptoms. The SCA7 repeats increased in length in successive generations. Normal alleles had from four to 18 repeats, with 10 repeats being the most common allele.
常染色体显性遗传性小脑共济失调伴视网膜变性（ADCAII）先前通过连锁分析研究被定位到3号染色体p12 - p21.1区域（SCA7）。近期的定位克隆研究发现了一个新基因SCA7，该基因含有一个可翻译的CAG重复序列，在SCA7患者中发生了扩增。我们从跨越SCA7候选区域的酵母人工染色体（YAC）克隆重叠群中克隆了SCA7基因。通过基因组测序和基于黏粒的外显子捕获相结合的方法，鉴定出了两个表达序列标签。对相应cDNA克隆进行测序并通过RT - PCR分析确定了全长SCA7 cDNA。我们的序列数据共同确定了SCA7基因前两个编码外显子的内含子/外显子边界，其中第一个外显子包含扩增的CAG重复序列。此外，与已发表的SCA7 cDNA进行序列比较，在SCA7基因的5'-UTR区域又鉴定出一个推定的外显子。SCA7基因被定位在YAC重叠群上D3S1600和D3S1287之间2.5 cM的区间内。在一个比利时的SCA7家系中，扩增的等位基因长度范围从38到至少55个重复，等位基因长度与ADCAII症状的发病年龄呈负相关。SCA7重复序列在连续几代中长度增加。正常等位基因有4到18个重复，其中10个重复是最常见的等位基因。
