Matsumura R, Takayanagi T, Fujimoto Y, Murata K, Mano Y, Horikawa H, Chuma T
Department of Neurology, Nara Medical University, Japan.
J Neurol Sci. 1996 Jul;139(1):52-7.
Trinucleotide repeat expansion in the Machado-Joseph disease (MJD) gene has been found in 26 patients from 20 unrelated Japanese families. Expanded alleles had 68 to 84 repeats, whereas normal alleles had 14 to 37 repeats. The age of onset was inversely correlated with the repeat length. To evaluate in detail the relationship between the repeat length and clinical features, we subdivided the 26 patients into three groups on the basis of the repeat length (group 1, 78 repeats or more; group 2, 74 to 77 repeats; group 3, 73 repeats or less). Group 1 and group 2 had common features of spasticity, hyperreflexia, Babinski sign, bulging eyes, facial myokymia and extrapyramidal signs as well as cerebellar ataxia and ophthalmoplegia. It should be noted that group 1 showed more prominent pyramidal and extrapyramidal signs than group 2. In contrast, group 3 showed hypotonia, hyporeflexia and sensory disturbance in addition to cerebellar ataxia and ophthalmoplegia. These findings suggest that the repeat length plays an important role in phenotypic variation. DNA analysis for the MJD mutation was clearly useful for making an accurate diagnosis in patients without bulging eyes, facial myokymia, dystonia or marked spasticity.
在来自20个不相关日本家庭的26名患者中发现了马查多-约瑟夫病（MJD）基因中的三核苷酸重复序列扩增。扩增的等位基因有68至84个重复序列，而正常等位基因有14至37个重复序列。发病年龄与重复序列长度呈负相关。为了详细评估重复序列长度与临床特征之间的关系，我们根据重复序列长度将26名患者分为三组（第1组，78个或更多重复序列；第2组，74至77个重复序列；第3组，73个或更少重复序列）。第1组和第2组有共同特征，包括痉挛、反射亢进、巴宾斯基征、突眼、面部肌束震颤和锥体外系体征，以及小脑共济失调和眼肌麻痹。应当指出的是，第1组的锥体和锥体外系体征比第2组更明显。相比之下，第3组除小脑共济失调和眼肌麻痹外，还表现为肌张力减退、反射减退和感觉障碍。这些发现表明重复序列长度在表型变异中起重要作用。对MJD突变进行DNA分析对于准确诊断没有突眼、面部肌束震颤、肌张力障碍或明显痉挛的患者显然是有用的。
