Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes.
Dissecting the clinical heterogeneity of autism spectrum disorders through defined genotypes.
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DOI：
10.1371/journal.pone.0010887
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发表时间：
2010-05-28
期刊：
影响因子：
3.7
通讯作者：
Vorstman J
中科院分区：
文献类型：
--
作者：
Bruining H;de Sonneville L;Swaab H;de Jonge M;Kas M;van Engeland H;Vorstman J
自闭症谱系障碍（ASD）的病因在很大程度上是由不同的遗传因素的可变影响。这种遗传异质性可能是解释自闭症谱系障碍临床异质性的一个因素。在这里，第一次尝试是评估是否遗传上更同质的ASD组与减少表型异质性相对于他们的自闭症症状谱。将患有22 q11缺失综合征（22 q11 DS）的ASD受试者和患有Klinefelter综合征（KS）的ASD受试者的自闭症表型与大（遗传）异质性ASD样本的症状特征进行统计学比较。自闭症诊断访谈修订（ADI-R）变量被输入不同的统计分析，以评估症状同质性的差异和区分组特异性ASD症状特征的可行性。结果显示，与异质性ASD样本相比，两个遗传性疾病ASD组的症状同质性显著较高。此外，22 q11-ASD和KS-ASD和特发性ASD表型之间的强大的歧视是可行的基础上减少自闭症量表和症状的数量。KS-ASD和22 q11 DS-ASD之间在区分子量表和症状方面缺乏重叠，这表明他们的自闭症症状特征集中在一般ASD人群中存在的特征的总诊断空间中的不同点周围。目前的研究结果表明，当从特发性ASD人群中提取基于特定基因型的亚组时，ASD的临床异质性可能会降低。目前广泛使用的ADI-R策略为评估基因型-表型ASD关系提供了相对直接的可能性。鉴于越来越多的证据表明，在相当大比例的ASD人群中存在影响巨大的遗传变异，逆转表型策略变得更加可行。
The etiology of autism spectrum disorders (ASD) is largely determined by different genetic factors of variable impact. This genetic heterogeneity could be a factor to explain the clinical heterogeneity of autism spectrum disorders. Here, a first attempt is made to assess whether genetically more homogeneous ASD groups are associated with decreased phenotypic heterogeneity with respect to their autistic symptom profile. The autistic phenotypes of ASD subjects with 22q11 deletion syndrome (22q11DS) and ASD subjects with Klinefelter Syndrome (KS) were statistically compared to the symptom profile of a large (genetically) heterogeneous ASD sample. Autism diagnostic interview-revised (ADI-R) variables were entered in different statistical analyses to assess differences in symptom homogeneity and the feasibility of discrimination of group-specific ASD-symptom profiles. The results showed substantially higher symptom homogeneity in both the genetic disorder ASD groups in comparison to the heterogeneous ASD sample. In addition, a robust discrimination between 22q11-ASD and KS-ASD and idiopathic ASD phenotypes was feasible on the basis of a reduced number of autistic scales and symptoms. The lack of overlap in discriminating subscales and symptoms between KS-ASD and 22q11DS-ASD suggests that their autistic symptom profiles cluster around different points in the total diagnostic space of profiles present in the general ASD population. The findings of the current study indicate that the clinical heterogeneity of ASDs may be reduced when subgroups based on a specific genotype are extracted from the idiopathic ASD population. The current strategy involving the widely used ADI-R offers a relatively straightforward possibility for assessing genotype-phenotype ASD relationships. Reverse phenotype strategies are becoming more feasible, given the accumulating evidence for the existence of genetic variants of large effect in a substantial proportion of the ASD population.
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