CAJ | 학술논문

目的通过对先天性高胰岛素血症患儿家系ABCC8、KCNJ11及GLUD1基因的突变分析,探讨先天性高胰岛素血症的遗传发病机制.方法选取2008年11月至2012年2月北京儿童医院收治的11例临床诊断为先天性高胰岛素血症的患儿及其家系为研究对象,其中男7例,女4例.应用PCR DNA直接测序技术对11个患儿的家系ABCC8基因的39个外显子区、KCNJ11基因的非翻译区及外显子区以及GLUD1基因的第6、7、10、11、12外显子区进行测序分析.结果 11例患儿家系中,病例1及其父亲携带ABCC8基因P629PfsX17杂合突变；病例4及其父亲携带ABCC8基因W288X杂合突变；病例5携带ABCC8基因A640V和Q1196x杂合突变,而其父亲仅携带ABCC8基因Q1196x杂合突变；病例6及其父亲携带GLUD1基因R269H杂合突变；上述4例患儿母亲相应基因位点均正常.另7例患儿及其父母并未检测出上述3种基因突变.结论 ABCC8基因突变是导致中国儿童先天性高胰岛素血症发病的主要致病机制.在中国人中,ABCC8基因的P629PfsX17、W288X、A640V、Q1196x杂合突变,GLUD1基因的R269H杂合突变可以导致先天性高胰岛素血症的发生,其遗传方式可为父系遗传或新生突变.
목적 통과대선천성고이도소혈증환인가계ABCC8、KCNJ11급GLUD1기인적돌변분석,탐토선천성고이도소혈증적유전발병궤제.방법 선취2008년11월지2012년2월북경인동의원수치적11례림상진단위선천성고이도소혈증적환인급기가계위연구대상,기중남7례,녀4례.응용PCR DNA직접측서기술대11개환인적가계ABCC8기인적39개외현자구、KCNJ11기인적비번역구급외현자구이급GLUD1기인적제6、7、10、11、12외현자구진행측서분석.결과 11례환인가계중,병례1급기부친휴대ABCC8기인P629PfsX17잡합돌변；병례4급기부친휴대ABCC8기인W288X잡합돌변；병례5휴대ABCC8기인A640V화Q1196x잡합돌변,이기부친부휴대ABCC8기인Q1196x잡합돌변；병례6급기부친휴대GLUD1기인R269H잡합돌변；상술4례환인모친상응기인위점균정상.령7례환인급기부모병미검측출상술3충기인돌변.결론 ABCC8기인돌변시도치중국인동선천성고이도소혈증발병적주요치병궤제.재중국인중,ABCC8기인적P629PfsX17、W288X、A640V、Q1196x잡합돌변,GLUD1기인적R269H잡합돌변가이도치선천성고이도소혈증적발생,기유전방식가위부계유전혹신생돌변.
Objective To explore the ABCC8,KCNJ11,and GLUD1 gene mutations of the 11 patients diagnosed as congenital hyperinsulinism(CHI).Methods A total of 11 CHI children hospitalized in Beijing Children's Hospital from November 2008 to February 2012 and their parents were chosen as the study subjects.Direct sequencing of PCR-DNA was used to analyze the 39 exons of ABCC8 gene,nontranslational region and exon of KCNJ11 gene and 6,7,10,11 and 12 exons of GLUD1 gene.Results An P629PfsX17 heterozygous mutation of ABCC8 gene was detected in case 1 and his father,an W288X heterozygous mutation of ABCC8 gene was detected in case 4 and his father,A640V and Q1196X mutations in ABCC8 gene in case 5 whose father only carried the Q1196X mutation.In case 6 and his father,an R269H mutation was found in GLUD1 gene.The genotype of 4 children's mothers was normal.No mutations were found in other 7 patients and their parents.Conclusions The ABCC8 gene mutations are the main pathogenic mechanisms of Chinese children with CHI.In Chinese,P629PfsX17,W288X,A640V and Q1196X heterozygous mutation of ABCC8 gene and R269H heterozygous mutation of GLUD1 gene may lead to CHI.The inheritance mode of the mutations may be paternally or de novo.