Kramer P L, Heiman G A, Gasser T, Ozelius L J, de Leon D, Brin M F, Burke R E, Hewett J, Hunt A L, Moskowitz C
Department of Neurology, Oregon Health Sciences University, Portland 97201.
Am J Hum Genet. 1994 Sep;55(3):468-75.
Idiopathic torsion dystonia (ITD) is characterized by involuntary twisting movements and postures. A gene for this disorder, DYT1, was mapped to chromosome 9q34 in 12 Ashkenazi Jewish (AJ) families and one large non-Jewish kindred. In the AJ population, strong linkage disequilibrium exists between DYT1 and adjacent markers within a 2-cM region. The associated haplotype occurs in > 90% of early limb-onset AJ cases. We examined seven non-Jewish ITD families of northern European and French Canadian descent to determine the extent to which early-onset ITD in non-Jews maps to DYT1. Results are consistent with linkage to the DYT1 region. Affected individuals in these families are clinically similar to the AJ cases; i.e., the site of onset is predominantly in the limbs and at least one individual in each pedigree had onset before age 12 years. None carries the AJ haplotype; therefore, they probably represent different mutations in the DYT1 gene. The two French Canadian families, however, display the same haplotype. Estimates of penetrance in non-Jewish families range from .40 to .75. We identified disease gene carriers and, with adjustments for age at onset, obtained a direct estimate of penetrance of .46. This is consistent with estimates of 30%-40% in the AJ population. Two other non-Jewish families with atypical ITD (later onset and/or cranial or cervical involvement) are not linked to DYT1, which indicates involvement of other genes in dystonia.
特发性扭转性肌张力障碍（ITD）的特征为不自主的扭转运动和姿势。1993年，在12个阿什肯纳兹犹太（AJ）家族和一个非犹太大家族中，将该疾病的一个基因DYT1定位于9号染色体长臂3区4带。在AJ人群中，DYT1与2厘摩区域内的相邻标记之间存在强连锁不平衡。相关单倍型出现在90%以上的早发性AJ病例中。我们研究了7个北欧和法裔加拿大血统的非犹太ITD家族，以确定非犹太人早发性ITD定位于DYT1的程度。结果与DYT1区域连锁一致。这些家族中的受累个体在临床上与AJ病例相似；即发病部位主要在四肢，每个家系中至少有一人在12岁之前发病。没有人携带AJ单倍型；因此，他们可能代表DYT1基因中的不同突变。然而，两个法裔加拿大家族显示相同的单倍型。非犹太家族的外显率估计范围为0.40至0.75。我们识别出疾病基因携带者，并对发病年龄进行调整后，直接估计出外显率为0.46。这与AJ人群中30%-40%的估计值一致。另外两个患有非典型ITD（发病较晚和/或有头颅或颈部受累）的非犹太家族与DYT1不连锁，这表明肌张力障碍涉及其他基因。
