Twist E C, Farrer L A, Macleod P M, Radvany J, Chamberlain S, Rosenberg R N, Rouleau G A
Centre for Research in Neuroscience, McGill University, Montreal, Canada.
Hum Genet. 1994 Mar;93(3):335-8. doi: 10.1007/BF00212034.
Machado Joseph disease (MJD) is a progressive, spinocerebellar ataxia (SCA) with an autosomal dominant mode of inheritance and almost complete penetrance. Clinically, it is difficult to distinguish it from other autosomal dominantly inherited ataxias, and it has been suggested that MJD may be caused by an allelic variant of SCA. Exclusion of MJD from the SCA1 locus on chromosome 6p has previously been demonstrated. However, following the recent assignment of a second locus for spinocerebellar ataxia (SCA2) to chromosome 12q in a large Cuban kindred of Spanish origin, we have investigated linkage in MJD families using the two markers, D12S58 and PLA2, that flank this disease gene. The MJD locus was definitively excluded from an interval spanning approximately 70 cM, which includes these loci. These studies demonstrate that MJD and SCA2 are genetically distinct despite similarities in disease phenotype and ancestral origins of the patients. Thus, the as yet unmapped MJD locus represents a third SCA locus, providing further evidence for genetic heterogeneity within these disorders.
马查多-约瑟夫病（MJD）是一种进行性脊髓小脑共济失调（SCA），呈常染色体显性遗传模式且几乎完全外显。临床上，很难将其与其他常染色体显性遗传共济失调区分开来，有人提出MJD可能是SCA的一个等位基因变体所致。先前已证明MJD不在6号染色体短臂上的SCA1基因座内。然而，最近在一个源自西班牙的古巴大家族中，将第二个脊髓小脑共济失调（SCA2）基因座定位于12号染色体长臂后，我们使用位于该疾病基因两侧的两个标记D12S58和PLA2，对MJD家系进行了连锁分析。MJD基因座被明确排除在一个跨度约70厘摩的区间之外，该区间包括这些基因座。这些研究表明，尽管患者的疾病表型和祖先来源相似，但MJD和SCA2在遗传上是不同的。因此，尚未定位的MJD基因座代表第三个SCA基因座，为这些疾病的遗传异质性提供了进一步证据。
