Silveira I, Coutinho P, Maciel P, Gaspar C, Hayes S, Dias A, Guimarães J, Loureiro L, Sequeiros J, Rouleau G A
Centre for Research in Neurosciences, McGill University and The Montreal General Hospital Research Institute, Québec, Canada.
Am J Med Genet. 1998 Mar 28;81(2):134-8. doi: 10.1002/(sici)1096-8628(19980328)81:2<134::aid-ajmg3>3.0.co;2-w.
The spinocerebellar ataxias (SCAs) are clinically and genetically a heterogeneous group of neurodegenerative disorders. To date, eight different loci causing SCA have been identified: SCA1, SCA2, Machado-Joseph disease (MJD)/SCA3, SCA4, SCA5, SCA6, SCA7, and dentatorubropallidoluysian atrophy (DRPLA). Expansion of a CAG repeat in the disease genes has been found in five of these disorders. To estimate the relative frequencies of the SCA1, DRPLA, MJD, SCA2, and SCA6 mutations among Portuguese ataxia patients, we collected DNA samples from 48 ataxia families and performed polymerase chain reaction (PCR) amplification of the CAG repeat mutations on chromosomes 6p, 12p, 14q, 12q, and 19p, respectively. Fifty-five individuals belonging to 34 dominant families (74%) had an expanded CAG repeat at the MJD gene. In five individuals from two kindreds with a dominant pattern of inheritance (4%), an expanded CAG repeat at the SCA2 gene was found. In MJD patients, the normal allele size ranged from 13 to 41, whereas the mutant alleles contained 65 to 80 repeats. For the SCA2 patients, normal alleles had 22 or 23, while expanded alleles had between 36 and 47 CAG units. We did not find the SCA1, DRPLA, or SCA6 mutations in our group of families. The MJD mutation remains the most common cause of SCA in Portugal, while a small number of cases are caused by mutations at the SCA2 gene, and 22% are due to still unidentified genes.
脊髓小脑共济失调（SCAs）在临床和遗传学上是一组异质性神经退行性疾病。迄今为止，已鉴定出八个导致SCA的不同基因座：SCA1、SCA2、马查多-约瑟夫病（MJD）/SCA3、SCA4、SCA5、SCA6、SCA7和齿状核红核苍白球路易体萎缩症（DRPLA）。在其中五种疾病中发现了疾病基因中CAG重复序列的扩增。为了估计葡萄牙共济失调患者中SCA1、DRPLA、MJD、SCA2和SCA6突变的相对频率，我们从48个共济失调家族中收集了DNA样本，并分别对6号染色体p臂、12号染色体p臂、14号染色体q臂、12号染色体q臂和19号染色体p臂上的CAG重复突变进行了聚合酶链反应（PCR）扩增。属于34个显性家族的55名个体（74%）在MJD基因处有CAG重复序列扩增。在两个具有显性遗传模式的家族中的5名个体（4%）中，发现了SCA2基因处的CAG重复序列扩增。在MJD患者中，正常等位基因大小范围为13至41，而突变等位基因包含65至80个重复序列。对于SCA2患者，正常等位基因有22或23个，而扩增后的等位基因有36至47个CAG单位。在我们的家族组中未发现SCA1、DRPLA或SCA6突变。MJD突变仍然是葡萄牙SCA最常见的病因，而少数病例由SCA2基因的突变引起，22%的病例病因仍不明。
