Consortium study of search for susceptibility genes of pervasive developmental disorder

点击翻译按钮获取中文摘要

This consortium study aimed to detect susceptibility genes of pervasive developmental disorders (PDD) including autism. We are recruiting PDD patients and the families, and thus far collected more than 300 hundred DNA samples of autism and other PDD patients, with the families' DNA in 240 patients. We analyzed candidate genes on the long-arm regions of choromosomes 2, 7 and 15 using the sample. The most extensively investigated were the genes on the chromosome 7 region, including TAC1, NPTX2, RELN, LAMB1, LAMB4, NRCAM, S-SCAM, FOXP2, PTPRZ1, WNT2, NPTX2 and other. We observed a significant association of the NRCAM polymorphisms, but no association of other genes, with PDD. In addition, we searched for a mutation in exons of a neuroligin-related molecule in PDD subjects, but no mutation has been found thus far. We also studied the Histidine region of the HOXA1 gene and found a novel polymorphism in autism patients. While the polymorphism finally proved to be not associated with autism, it caused a disturbance of cellular function which may lead to abnormal neuronal differentiation. It may be interesting to study what kind of developmental disorder the polymorphism is associated with. Other studies we conducted were an examination of the FMR triplet-repeat polymorphism (not the abnormal expansion), which was not associate with autism as a result, and an investigation of the allele-specific expression of MECP2 gene in lymphoblast from subjects with Rett syndrome. Mutation was observed in the methylated CpG binding domain of the gene in a half of the subjects. The mutation allele was not expressed however in most of the lymphoblast with the mutation.