青少年发病的成人糖尿病7型新突变的可能位点

A potential novel mutation site for type 7 maturity-onset diabetes of the young

目的通过对一个高度怀疑为青少年发病的成人糖尿病7型(MODY7)家系进行信息收集及基因检测,寻找其基因突变位点,并探讨其临床特点。方法对1例病程20年、长期胰岛素治疗但血糖控制不佳、无酮症倾向、有3代糖尿病家族史的28岁女性患者进行基因检测,发现其携带KLF11基因变异,遂对其家系进行调查,收集家庭成员相关临床资料,并进行致病基因检测。基因检测方法为:首先对先证者采用芯片捕获高通量测序方法寻找致病基因,然后使用Sanger测序技术验证基因突变位点,并对其他家系成员使用Sanger测序技术筛查有无相同基因突变位点。结果该家系共检出2例成员存在KLF11基因杂合突变c.920C>T(编码区第920号核苷酸由胞嘧啶变异为胸腺嘧啶),导致氨基酸改变p.P307L(第307号氨基酸由脯氨酸变异为亮氨酸),为错义突变。这与其临床被诊断为糖尿病相符合。结论本研究的家系为KLF11基因c.920C>T(p.P307L)错义突变导致糖尿病家系,该突变位点可能是MODY7新突变位点。

Objective To search for the potential novel mutation site and to discuss related clinical characteristics by collecting detailed information and testing the gene of a family with highly suspected type 7 maturity-onset diabetes of the young(MODY7).Methods The gene test was conducted in a 28-year-old female patient with a 20-year course of non-ketosis-prone diabetes,with non-effective long-term insulin treatment,and a 3-generation family history of diabetes,and the patient was found to carry KLF11 gene mutation.Thus,the clinical data of family members were collected and investigated,and the pathogenic gene was tested.Firstly,the proband was searched for pathogenic genes by chip-capture high-throughput sequencing method.Then the mutation sites were verified by Sanger sequencing technology,and other family members were searched for the same mutation sites by the Sanger sequencing technology.Results A total of two members of the family was found to have heterozygous mutation of KLF11 gene:c.920C>T(No.920 nucleotide of the coding region mutated from cytosine to thymine),resulting in the change of corresponding amino acid p.P307L(No.307 amino acid changed from proline to leucine),which was a missense mutation and was consistent with their clinical diagnosis of diabetes.Conclusions The family in this study had a family history of diabetes caused by the missense mutation of KLF11 gene.This is the first report of the mutation site of c.920C>T(p.P307l),which may be a new mutation site of MODY7.