Loesch Danuta Z, Bui Quang M, Dissanayake Cheryl, Clifford Sally, Gould Emma, Bulhak-Paterson Danuta, Tassone Flora, Taylor Annette K, Hessl David, Hagerman Randi, Huggins Richard M
School of Psychological Science, La Trobe University, Melbourne, VIC, Australia.
Neurosci Biobehav Rev. 2007;31(3):315-26. doi: 10.1016/j.neubiorev.2006.09.007. Epub 2006 Nov 9.
The distributions of scores for autistic behaviours obtained from the Autism Diagnostic Observation Scale-Generic (ADOS-G) were investigated in 147 males and females affected with the full mutation in the fragile X mental retardation 1 (FMR1) gene, in 59 individuals with the premutation, and in 42 non-fragile X relatives, aged 4-70 years. The scores representing communication and social interaction were continuously distributed across the two fragile X groups, and they were significantly elevated compared with the non-fragile X controls. Strong relationships were found between both these scores and FMRP deficits, but they became insignificant for social interaction, and the sum of social interaction and communication scores, when FSIQ was included as another predictor of autism scores. Other significant predictors of these scores in both sexes were those executive skills which related to verbal fluency, and to the regulation and control of motor behaviour. Overall, our data have shown that cognitive impairment, especially of verbal skills, best explains the comorbidity of autism and fragile X. This implies some more fundamental perturbations of specific neural connections which are essential for both specific behaviours and cognition. We also emphasize that FXS offers a unique molecular model for autism since FMRP regulates the translation of many other genes involved in synaptic formation and plasticity which should be natural targets for further exploration.
对147名患有脆性X智力低下1（FMR1）基因完全突变的男性和女性、59名携带前突变的个体以及42名4至70岁的非脆性X亲属进行了研究，以调查从孤独症诊断观察量表通用版（ADOS - G）获得的孤独症行为评分分布情况。代表沟通和社交互动的评分在两个脆性X组中呈连续分布，与非脆性X对照组相比显著升高。在这两个评分与脆性X智力低下蛋白（FMRP）缺陷之间发现了很强的相关性，但当将全量表智商（FSIQ）作为孤独症评分的另一个预测因子时，社交互动以及社交互动与沟通评分之和的相关性变得不显著。在男女两性中，这些评分的其他显著预测因子是那些与言语流畅性以及运动行为的调节和控制相关的执行技能。总体而言，我们的数据表明，认知障碍，尤其是言语技能方面的障碍，最能解释孤独症与脆性X综合征的共病情况。这意味着对特定神经连接存在一些更根本的扰动，而这些神经连接对于特定行为和认知都是必不可少的。我们还强调，脆性X综合征为孤独症提供了一个独特的分子模型，因为FMRP调节许多其他参与突触形成和可塑性的基因的翻译，这些基因应是进一步探索的天然靶点。
