Familial symptom domains in monozygotic siblings with autism
Familial symptom domains in monozygotic siblings with autism
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DOI：
10.1002/ajmg.b.30011
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发表时间：
2004-08-15
影响因子：
2.8
通讯作者：
Silverman, JM
中科院分区：
文献类型：
--
作者：
Kolevzon, A;Smith, CJ;Silverman, JM
孤独症的特征在于三个症状领域（社交互动受损，沟通障碍和重复行为），这些症状在人群中的临床表现差异很大。然而，在有多个受影响成员的家庭中，存在症状变异性方面的不一致发现。减少家族内变异是特别重要的，因为它支持遗传异质性在自闭症的传播的基础模型，和家庭临床亚型的鉴定可以用来选择更多的同质样本在未来的连锁分析。本研究旨在探讨是否有自闭症的具体特点，显示减少16个家庭的同卵兄弟姐妹自闭症一致的方差。家族性的证据被定义为同卵同胞之间相比，同胞之间症状水平的差异显著降低。使用回归分析，我们证明了自闭症三个主要症状领域中的两个在同卵同胞中的症状显著聚集：沟通和社会互动障碍表现出显着的熟悉性。在重复行为领域内，只有有限的利益和专注于部分对象的类别显示出减少兄弟姐妹之间的差异。此外，除了社会和行为领域之间的负相关外，偏相关系数并没有显示出家庭内不同症状领域之间的显着关联，这表明自闭症的临床特征水平可能是主要独立遗传特征的结果。由于假定的遗传异质性和广泛的临床变化，在自闭症和其他广泛的发展障碍，选择先证者根据特定的功能，已知显示减少家庭内的差异可能会提供更多的同质样本的遗传分析和加强的力量，以检测特定的基因参与自闭症。(C)2004 Wiley-Liss，Inc.
Autism is characterized by a triad of symptom domains (impaired social interaction, communication deficits, and repetitive behaviors) that vary significantly in their clinical presentation across the population. Within families with more than one affected member, however, discrepant findings exist with regard to symptom variability. Reduced intrafamily variance is of particular importance because it supports an underlying model of genetic heterogeneity in the transmission of autism, and the identification of familial clinical subtypes can be used to select more homogeneous samples for linkage analysis in the future. This study examines whether there are specific features of autism that show decreased variance within 16 families with monozygotic siblings concordant for autism. Evidence for familiality was defined as significantly decreased variance of symptom levels within monozygotic siblingships as compared to between siblingships. Using regression analysis, we demonstrated Significant aggregation of symptoms within monozygotic siblingships for two of the three main symptom domains in autism: impairments in communication and social interaction showed significant familiality. Within the repetitive behavior domain, only the categories of circumscribed interests and preoccupation with part-objects showed reduced variance within siblingships. In addition, with the exception of a negative association between the social and behavior domains, partial correlation coefficients did not reveal significant associations between the levels of different symptom domains within families, suggesting that the levels of clinical features seen in autism may be a result of mainly independent genetic traits. Because of presumed genetic heterogeneity and the wide clinical variation seen in autism and other pervasive developmental disorders, selecting probands according to specific features known to show reduced variance within families may provide more homogeneous samples for genetic analysis and strengthen the power to detect the specific genes involved in autism. (C) 2004 Wiley-Liss, Inc.