St George-Hyslop P, Rogaeva E, Huterer J, Tsuda T, Santos J, Haines J L, Schlumpf K, Rogaev E I, Liang Y, McLachlan D R
Department of Medicine, University of Toronto, Ontario, Canada.
Am J Hum Genet. 1994 Jul;55(1):120-5.
A locus for Machado-Joseph disease (MJD) has recently been mapped to a 30-cM region of chromosome 14q in five pedigrees of Japanese descent. MJD is a clinically pleomorphic neurodegenerative disease that was originally described in subjects of Azorean descent. In light of the nonallelic heterogeneity in other inherited spinocerebellar ataxias, we were interested to determine if the MJD phenotype in Japanese and Azorean pedigrees arose from mutations at the same locus. We provide evidence that MJD in five pedigrees of Azorean descent is also linked to chromosome 14q in an 18-cM region between the markers D14S67 and AACT (multipoint lod score +7.00 near D14S81). We also report molecular evidence for homozygosity at the MJD locus in an MJD-affected subject with severe, early-onset symptoms. These observations confirm the initial report of linkage of MJD to chromosome 14; suggest that MJD in Japanese and Azorean subjects may represent allelic or identical mutations at the same locus; and provide one possible explanation (MJD gene dosage) for the observed phenotypic heterogeneity in this disease.
最近，在五个日本血统的家系中，马查多-约瑟夫病（MJD）的一个基因座已被定位到14号染色体长臂的一个30厘摩区域。MJD是一种临床多形性神经退行性疾病，最初在亚速尔群岛血统的人群中被描述。鉴于其他遗传性脊髓小脑共济失调存在非等位基因异质性，我们有兴趣确定日本和亚速尔群岛家系中的MJD表型是否由同一基因座的突变引起。我们提供的证据表明，五个亚速尔群岛血统家系中的MJD也与14号染色体长臂在标记D14S67和AACT之间的一个18厘摩区域连锁（在D14S81附近多点对数计分+7.00）。我们还报告了一名患有严重早发症状的MJD患者在MJD基因座纯合的分子证据。这些观察结果证实了MJD与14号染色体连锁的最初报告；表明日本和亚速尔群岛人群中的MJD可能代表同一基因座的等位基因或相同突变；并为该疾病中观察到的表型异质性提供了一种可能的解释（MJD基因剂量）。
