Ma Shaochun, Davis Thomas L, Blair Marcia A, Fang John Y, Bradford Yuki, Haines Jonathan L, Hedera Peter
Department of Neurology, Vanderbilt University, Nashville, Tennessee, USA.
Mov Disord. 2006 Sep;21(9):1368-74. doi: 10.1002/mds.20950.
A positive family history is present in many patients with essential tremor (ET), but twin studies and segregation analysis have suggested that ET is not entirely a genetic disorder. Two genetic loci have been identified in autosomal dominant (AD) ET and polymorphisms in the DRD3 and HS1-BP3 genes have been proposed as the possible susceptibility factors for ET. There is also evidence for further genetic heterogeneity. We evaluated 4 unrelated large kindreds with ET with an apparent AD mode of transmission. Each kindred spanned at least 3 generations and contained at least 13 living affected subjects who met criteria for definitive ET. None of the pedigrees had evidence for inheritance of ET from both parents. Known genetic ET loci were excluded in these families. We detected a preferential transmission of ET in every kindred and the proportion of affected offspring varied from 75% to 90% (P < 0.05) in the generations with complete ascertainment. Our data indicate that non-Mendelian preferential transmission of an affected allele is a feature in many ET kindreds with multiple affected members and an apparent AD mode of inheritance. ET may have a complex etiology. Additional genetic models need to be considered, including an interaction of susceptibility genes and environmental risk factors.
许多特发性震颤（ET）患者存在阳性家族史，但双生子研究和系谱分析表明，ET并非完全是一种遗传性疾病。在常染色体显性（AD）ET中已鉴定出两个基因位点，并且已提出DRD3和HS1 - BP3基因中的多态性可能是ET的易感性因素。也有证据表明存在进一步的遗传异质性。我们评估了4个不相关的、具有明显AD遗传模式的ET大家族。每个家族至少跨越3代，并且包含至少13名符合明确ET标准的在世受累者。这些家系中没有证据表明ET是由父母双方遗传而来。在这些家族中排除了已知的遗传性ET位点。我们在每个家族中均检测到ET的优先传递，在完全确定的几代人中，受累后代的比例从75%到90%不等（P < 0.05）。我们的数据表明，受累等位基因的非孟德尔式优先传递是许多有多个受累成员且具有明显AD遗传模式的ET家族的一个特征。ET可能具有复杂的病因。需要考虑其他遗传模式，包括易感基因与环境风险因素的相互作用。
