Haberhausen G, Damian M S, Leweke F, Müller U
Institut für Humangenetik, Justus-Liebig-Universität, Giessen, Germany.
J Neurol Sci. 1995 Sep;132(1):71-5. doi: 10.1016/0022-510x(95)90927-i.
Spinocerebellar ataxia, type 3 (SCA3) and Machado-Joseph disease (MJD) are two clinically distinct representatives of the heterogeneous group of autosomal dominant cerebellar ataxias. Assignment of the disease genes to the same region of the long arm of chromosome 14 in both SCA3 and MJD suggested that these two disorders are genetically identical. The recent identification of a trinucleotide (CAG) repeat expansion in a gene underlying MJD facilitates assessment of this hypothesis. We analysed the MJD gene in members of a family with characteristic features of SCA3 and no symptoms typical of MJD. We found the same trinucleotide repeat expansion within the gene that was previously described in patients with MJD. The findings demonstrate that SCA3 and MJD are genetically identical in spite of their pronounced clinical differences. Furthermore, we demonstrate a striking variation in the copy number of the CAG repeat among affected members of the same family.
脊髓小脑共济失调3型（SCA3）和马查多-约瑟夫病（MJD）是常染色体显性小脑共济失调异质性组中的两种临床不同代表。在SCA3和MJD中，疾病基因都定位于14号染色体长臂的同一区域，这表明这两种疾病在遗传上是相同的。最近在MJD相关基因中发现的三核苷酸（CAG）重复扩增有助于对这一假说进行评估。我们分析了一个具有SCA3特征但无MJD典型症状的家族成员的MJD基因。我们在该基因中发现了与先前MJD患者中描述的相同的三核苷酸重复扩增。这些发现表明，尽管SCA3和MJD在临床上有明显差异，但它们在遗传上是相同的。此外，我们还证明了同一家族受影响成员中CAG重复拷贝数存在显著差异。
