一例孤独症谱系障碍男童DIAPH3基因的突变分析

Analysis of DIAPH3 gene mutation in a boy with autism spectrum disorder

目的分析1例孤独症谱系障碍（autismspectrumdisorder，ASD）患儿的临床表现和基因突变，探讨DIAPH3基因的新发突变与ASD发病风险及发病机制的关系。方法首先对患儿进行神经检查、精神评估等，然后抽取患儿及其父母的外周血行全外显子组测序，以明确致病基因突变。结果先证者的临床评估提示患者属于典型ASD，通过全外显子组测序确认4个候选基因，包括TUT1、DIAPH3、RELN和SETD2。发现DIAPH3基因第18外显子C．2156T〉C（p1719T）错义突变，该突变位于FH2保守结构域；检测到TuT1无义突变，该突变可能破坏了TUT1／Lin28A调节通路的正常功能。发现RELN基因3个同义突变；SETD2基因第15外显子c．6895G〉A（p．G2299R）错义突变。患儿父母的Sanger测序结果未检测到DIAPH3与SETD2的错义突变，表明患儿的两个错义突变均为新生突变。结论DIAPH3与SETD2的错义突变可能增加患自闭症的风险。与DIAPH3和SETD2突变相关的神经发育与神经突触形成受损可能是ASD潜在的发病机制。

Objective To analyze the clinical manifestations and gene mutation of a 6 year old boy with autism spectrum disorders （ASD）. Methods Peripheral blood of the boy and his parents were subjected to genetic testing. Results The patient was diagnosed with typical autism. Exome sequencing has identified mutations of four candidate genes, namely TUT1, DIAPH3, REELIN and SETD2, which were confirmed with Sanger sequencing. Analysis of family members confirmed that the missense mutations of DIAPH3 and SETD2 genes were of de novo origin. Conclusion Missense mutations of DIAPH3 and SETD2 genes may have contributed to the risk of ASD. Disrupted neurogenesis associated with such mutations mav have been the underlving mechanism for ASD.