Telenius H, Kremer H P, Theilmann J, Andrew S E, Almqvist E, Anvret M, Greenberg C, Greenberg J, Lucotte G, Squitieri F
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Hum Mol Genet. 1993 Oct;2(10):1535-40. doi: 10.1093/hmg/2.10.1535.
Juvenile Huntington disease (HD), characterised by onset of symptoms before the age of 20 with rigidity and intellectual decline, is associated with a predominance of affected fathers. In order to investigate the molecular basis for the observed parental effect, we have analysed the CAG trinucleotide repeat within the HD gene in 42 juvenile onset cases from 34 families. A highly significant correlation was found between the repeat length and age of onset (r = -0.86, p < 10(-7) and it was determined that the sex of transmitting parent was the major influence on CAG expansion leading to earlier onset. Neither the size of the parental upper allele, the age of parent at conception of juvenile onset child, nor the grandparental sex conferred a significant effect upon expansion. Affected sib pair analysis of CAG repeat length, however, revealed a high correlation (r = 0.91, p < 10(-7). Furthermore, analysis of nuclear and extended families showed a familial predisposition to juvenile onset disease. This study demonstrates that the sex of transmitting parent is the major influence on trinucleotide expansion and clinical features in juvenile Huntington disease.
青少年型亨廷顿舞蹈症（HD）的特征是在20岁之前出现症状，伴有僵硬和智力衰退，且患病父亲居多。为了研究观察到的亲代效应的分子基础，我们分析了来自34个家庭的42例青少年发病病例的HD基因中的CAG三核苷酸重复序列。发现重复序列长度与发病年龄之间存在高度显著的相关性（r = -0.86，p < 10^(-7)），并且确定传递亲代的性别是导致发病较早的CAG扩增的主要影响因素。亲代上一等位基因的大小、生育青少年发病子女时亲代的年龄以及祖父母的性别对扩增均无显著影响。然而，对CAG重复序列长度的患病同胞对分析显示出高度相关性（r = 0.91，p < 10^(-7)）。此外，对核心家庭和大家庭的分析表明青少年发病疾病存在家族易感性。这项研究表明，传递亲代的性别是青少年型亨廷顿舞蹈症中三核苷酸扩增和临床特征的主要影响因素。
