Pampanos Andreas, Volaki Konstantina, Kanavakis Emmanuel, Papandreou Ourania, Youroukos Sotiris, Thomaidis Loretta, Karkelis Savvas, Tzetis Maria, Kitsiou-Tzeli Sophia
Department of Medical Genetics, Medical School, University of Athens, Aghia Sophia Children's Hospital, Athens, Greece.
Genet Test Mol Biomarkers. 2009 Oct;13(5):611-5. doi: 10.1089/gtmb.2009.0005.
Autism is a neurodevelopmental disorder characterized by clinical, etiologic, and genetic heterogeneity. During the last decade, predisposing genes and genetic loci were under investigation. Recently, mutations in two X-linked neuroligin genes, neuroligin 3 (NLGN3) and neuroligin 4 (NLGN4), have been implicated in the pathogenesis of autism. In our ongoing survey, we screened 169 patients with autism for mutations linked with autism. In the preliminary study of specific exons of NLGN3 and NLGN4 genes, we identified the p.K378R substitution (c.1597 A > G) in exon 5 of the NLGN4 gene in a patient who was found to have mild autism and normal IQ at 3 years of age. The same mutation has previously been found in a patient with autism. It is important that, for the first time, a specific mutation in neuroligins is confirmed in a molecular screen in another homogeneous ethnic population. This finding further contributes to consideration of neuroligins as probable candidate genes for future molecular genetic studies, suggesting that a defect of synaptogenesis may predispose to autism.
自闭症是一种神经发育障碍，具有临床、病因和遗传异质性。在过去十年中，人们一直在研究相关的易感基因和基因位点。最近，两个X连锁的神经连接蛋白基因，即神经连接蛋白3（NLGN3）和神经连接蛋白4（NLGN4）的突变，被认为与自闭症的发病机制有关。在我们正在进行的调查中，我们对169名自闭症患者进行了与自闭症相关突变的筛查。在对NLGN3和NLGN4基因特定外显子的初步研究中，我们在一名3岁时被诊断为轻度自闭症且智商正常的患者的NLGN4基因第5外显子中鉴定出了p.K378R替代突变（c.1597 A > G）。此前在另一名自闭症患者中也发现了相同的突变。重要的是，首次在另一个同种族人群的分子筛查中证实了神经连接蛋白中的特定突变。这一发现进一步促使人们将神经连接蛋白视为未来分子遗传学研究中可能的候选基因，表明突触形成缺陷可能易患自闭症。
