DNAH2基因突变与一穴肛畸形相关性的初步研究  

The study of the association between DNAH2 mutations and persistent cloaca

作　　者：王琛[1] 王丽燕 李龙[3] 郑伟[3] Wang Chen;Wang Liyan;Li Long;Zheng Wei(Department of General Surgery, Heze Municipal Hospital, Heze 274000 , China;Department of Anesthesiology, Heze Municipal Hospital, Heze 274000 , China;Department of Pediatric Surgery, Capital Institute of Pediatrics, Beijing 100020, China)

机构地区：[1]菏泽市立医院普通外科,274000 [2]菏泽市立医院麻醉科,274000 [3]首都儿科研究所附属儿童医院普外科,北京100020

出　　处：《国际遗传学杂志》2019年第2期115-119,共5页International Journal of Genetics

基　　金：卫生部行业专项课题(201402007).

摘　　要：目的探讨基因丝动力蛋白(DNAH2)基因突变与一穴肛畸形形成相关性。方法选取4例一穴肛畸形核心家系和8例独立患者,采集术中标本及外周静脉血提取DNA,行全基因组外显子测序,筛选出致病DNAH2突变,以AdMax腺病毒干扰沉默人间质干细胞DNAH2基因进行功能验证,观察SHH信号传导通路下游靶基因SMO及Gli2蛋白表达变化。结果筛选出DNAH2基因的复合杂合非同义突变(p.Ser312Thr和p.Arg573Cys),沉默人间质干细胞DNAH2基因后可观察到细胞内SHH信号传导通路下游靶基因SMO及Gli2蛋白表达减弱。结论DNAH2基因复合杂合非同义突变(p.Ser312Thr和p.Arg573Cys)可能与一穴肛畸形发病相关,其遗传模式可能为复杂隐性遗传,具体的机制仍需进一步的动物基因敲除模型证实。Objective The aim of this study is to identify the association between the mutations of DNAH2 gene and human persistent cloaca (PC) in Chinese population. Methods Four cases of core family and eight independent patients were selected for whole exome sequencing, their clinical date was collected. Genomic DNA was extracted from peripheral blood and specimen. Whole exome sequencing was performed using CG Black Bird sequencing platform. Inheritance analysis were performed for de novo mutation and inherited recessive mutation. The AdMax adenovirus was used to silence DNAH2 gene of human mesenchymal stem cells (hMSC), and the expression of Smo and Gli2 proteins in SHH signaling pathway was observed by Western blotting. Results Compound heterozygous mutations of DNAH2 (p.Ser312Thr and p. Arg573Cys) were identified in a trio family. When DNAH2 gene was silenced in hSMC, the expression of Smo and Gli2 was observed to be decreased. Conclusion We used whole exome sequencing to identify two compound heterozygous mutations in DNAH2(p.Ser312Thr and p. Arg573Cys). Experimental model systems may be critical for elucidating the function of DNAH2 and the developmental pathways impacted by these mutations.

关 键 词：泄殖腔畸形 全基因组测序技术 基因突变 

分 类 号：R726.5[医药卫生—儿科]