Walkup J T, LaBuda M C, Singer H S, Brown J, Riddle M A, Hurko O
Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, USA.
Am J Hum Genet. 1996 Sep;59(3):684-93.
To investigate the transmission of Tourette syndrome (TS) and associated disorders within families, complex segregation analysis was performed on family study data obtained from 53 independently ascertained children and adolescents with TS and their 154 first-degree relatives. The results suggest that the susceptibility for TS is conveyed by a major locus in combination with a multifactorial background. Other models of inheritance were definitively rejected, including strictly polygenic models, all single major locus models, and mixed models with dominant and recessive major loci. The frequency of the TS susceptibility allele was estimated to be .01. The major locus accounts for over half of the phenotypic variance for TS, whereas the multifactorial background accounts for approximately 40% of phenotypic variance. Penetrance estimates suggest that all individuals homozygous for the susceptibility allele at the major locus are affected, whereas only 2.2% of males and 0.3% of females heterozygous at the major locus are affected. Of individuals affected with TS, approximately 62% are heterozygous and approximately 38% are homozygous at the major locus. While none of the families had two parents affected with TS, 19% of families had two parents affected with the broader, phenotype, which includes TS, chronic tic disorder, or obsessive-compulsive disorder.
为研究抽动秽语综合征（TS）及相关疾病在家族中的传递情况，对从53名独立确诊的TS儿童和青少年及其154名一级亲属获得的家族研究数据进行了复杂分离分析。结果表明，TS易感性由一个主要基因座与多因素背景共同传递。其他遗传模型被明确排除，包括严格的多基因模型、所有单主要基因座模型以及具有显性和隐性主要基因座的混合模型。TS易感等位基因的频率估计为0.01。主要基因座占TS表型变异的一半以上，而多因素背景约占表型变异的40%。外显率估计表明，主要基因座上所有易感等位基因纯合的个体均受影响，而主要基因座上杂合的男性仅2.2%、女性仅0.3%受影响。在受TS影响的个体中，主要基因座上约62%为杂合子，约38%为纯合子。虽然没有家庭的父母双方都患有TS，但19%的家庭父母双方患有更广泛的表型，包括TS、慢性抽动障碍或强迫症。
