CAJ | 학술논문

目的对27例婴幼儿糖尿病家系进行KCNJ11基因突变分析,对婴幼儿糖尿病的遗传发病机制进行初步探讨.方法选取2000年8月至2011年10月收治的婴幼儿糖尿病患儿27例为研究对象,其中男孩13例,女孩14例,起病年龄为出生后30 d～2岁7个月,用DNA提取试剂盒提取外周血基因组DNA,运用聚合酶链反应(PCR)技术扩增KCNJ11基因的外显子区,并用DNA直接测序技术对患儿家系的KCNJ11基因进行突变分析.结果在1例新生儿糖尿病患儿的KCNJ11基因中发现了一个15碱基对的碱基缺失(c.82-96del),该缺失导致Kir6.2蛋白相应5个氨基酸的缺失(A28-R32),患儿父母KCNJ11基因型正常,对该患儿进行了2周的格列本脲试验性治疗,结果显示治疗有效.本研究还在另1例1岁7个月发病的患儿及其父亲中发现了KCNJ11基因的1个杂合突变(c.1096G＞ T),该突变导致Kir6.2蛋白G366W突变.其余25例患儿均未发现KCNJ11基因突变.结论罕见的KCNJ11基因c.82-96del碱基缺失突变可导致新生儿糖尿病的发生.KCNJ11基因突变也可导致婴幼儿糖尿病的发生,其具体致病机制有待进一步的功能表达研究来证实.
목적 대27례영유인당뇨병가계진행KCNJ11기인돌변분석,대영유인당뇨병적유전발병궤제진행초보탐토.방법 선취2000년8월지2011년10월수치적영유인당뇨병환인27례위연구대상,기중남해13례,녀해14례,기병년령위출생후30 d～2세7개월,용DNA제취시제합제취외주혈기인조DNA,운용취합매련반응(PCR)기술확증KCNJ11기인적외현자구,병용DNA직접측서기술대환인가계적KCNJ11기인진행돌변분석.결과 재1례신생인당뇨병환인적KCNJ11기인중발현료일개15감기대적감기결실(c.82-96del),해결실도치Kir6.2단백상응5개안기산적결실(A28-R32),환인부모KCNJ11기인형정상,대해환인진행료2주적격렬본뇨시험성치료,결과현시치료유효.본연구환재령1례1세7개월발병적환인급기부친중발현료KCNJ11기인적1개잡합돌변(c.1096G＞ T),해돌변도치Kir6.2단백G366W돌변.기여25례환인균미발현KCNJ11기인돌변.결론 한견적KCNJ11기인c.82-96del감기결실돌변가도치신생인당뇨병적발생.KCNJ11기인돌변야가도치영유인당뇨병적발생,기구체치병궤제유대진일보적공능표체연구래증실.
Objective To analyze gene mutation on KCNJ11 gene in 27 patients with infancy and early childhood diabetes mellitus.Methods Total of 27 patients(13 boys and 14 girls) diagnosed with infancy or early childhood diabetes mellitus on 30 days to 2 year and 7 months after birth and their parents were chosen as subjects.TIANamp blood DNA kit techniques were used to extract genomic DNA from peripheral white blood cells,polymerase chain reaction(PCR) techniques were used to amplify the KCNJ11 gene,after which DNA direct assay techniques were used to analyze gene mutation on KCNJ11.Results A in-frame 15-bp KCNJ11 deletion was identified in a patient diagnosed with neonatal diabetes mellitus (c.82-96del),which resulted in 5 amine acids deletions (A28-R32),while no KCNJ11 deletions were found in her parents.The patient was responsive to the treatment of glibenclamide.A heterozygous c.1096G ＞ T (G366W) mutation was identified in a girl diagnosed with diabetes at 1 year and 7 months after birth,and her father carried the same mutation.No KCNJ11 mutations were found in other paitents.Conclusion The rare c.82-96del mutation on KCNJ11 can lead to neonatal diabetes mellitus.Also the mutation on KCNJ11 can lead to infancy and early childhood diabetes mellitus,while the onset mechanism is not clear.