Sasaki H
Department of Neurology, Hokkaido University School of Medicine, Sapporo, Japan.
Hokkaido Igaku Zasshi. 1997 Jan;72(1):13-20.
Hereditary spinocerebellar ataxia (SCA) is a cluster of genetically heterogeneous disorders, and was classified based on the mode of inheritance and clinicopathological features. Recent molecular genetic studies determined the locus of responsible mutation in 7 dominant SCAs ¿SCA1, SCA2, Machado-Joseph disease (SCA3), SCA4, SCA5, SCA7, DRPLA¿ and one recessive SCA ¿Friedreich's ataxia (FRDA)¿. Of these disorders, abnormal CAG repeat expansions were identified in the mutation of 5 dominant SCAs (SCA1, SCA2, MJD, DRPLA), and abnormal GAA repeat expansion in FRDA mutation. Thus, all these SCAs are members of "triplet repeat disorders". As found in other triplet repeat disorders, number of triplet repeat correlates with clinical severity and variety of clinical phenotypes: age at onset is inversely correlated with repeat length. Throughout the study for SCA gene mutation, we found SCA1, SCA2, and MJD in Hokkaido. More than half were MJD in our subjects, indicating that this disorder is the most prevalent in the dominant SCA seen in Hokkaido. The results of this molecular genetic study and their implication for understanding the variety of SCA phenotype are presented in this symposium.
遗传性脊髓小脑共济失调（SCA）是一组具有遗传异质性的疾病，根据遗传方式和临床病理特征进行分类。最近的分子遗传学研究确定了7种显性SCA（SCA1、SCA2、马查多-约瑟夫病（SCA3）、SCA4、SCA5、SCA7、齿状核红核苍白球路易体萎缩症（DRPLA））和1种隐性SCA（弗里德赖希共济失调（FRDA））的致病突变位点。在这些疾病中，5种显性SCA（SCA1、SCA2、MJD、DRPLA）的突变中发现了异常的CAG重复扩增，而在FRDA突变中发现了异常的GAA重复扩增。因此，所有这些SCA都是“三联体重复疾病”的成员。正如在其他三联体重复疾病中所发现的，三联体重复的数量与临床严重程度和临床表型的多样性相关：发病年龄与重复长度呈负相关。在对SCA基因突变的整个研究过程中，我们在北海道发现了SCA1、SCA2和MJD。在我们的研究对象中，超过一半是MJD，这表明这种疾病在北海道所见的显性SCA中最为普遍。本次研讨会将介绍这项分子遗传学研究的结果及其对理解SCA表型多样性的意义。
