Identification of HNF4A Mutation p.T130I and HNF1A Mutations p.I27L and p.S487N in a Han Chinese Family with Early-Onset Maternally Inherited Type 2 Diabetes.
Identification of HNF4A Mutation p.T130I and HNF1A Mutations p.I27L and p.S487N in a Han Chinese Family with Early-Onset Maternally Inherited Type 2 Diabetes.
复制标题
中国汉族早发母系遗传2型糖尿病家系中HNF4A突变p.T130I和HNF1A突变p.I27L和p.S487N的鉴定
DOI：
10.1155/2016/3582616
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发表时间：
2016
影响因子：
4.3
通讯作者：
Zhang YP
中科院分区：
文献类型：
--
作者：
Yang Y;Zhou TC;Liu YY;Li X;Wang WX;Irwin DM;Zhang YP
年轻人成熟型糖尿病（MODY）的特征在于25岁之前糖尿病的发病、阳性家族史、高遗传易感性、单基因突变和常染色体显性遗传模式。在这里，我们的目的是调查突变和表现型的一个汉族家庭与早发母系遗传2型糖尿病的特点。在该家族中进行了详细的临床评估和HNF 4 α、GCK、HNF-1α、IPF-1、HNF 1 β和NEUROD 1基因突变的遗传筛查。发现了一个HNF 4A突变（p.T130I）和两个HNF 1A多态性（p.I27L和p.S487N）。突变p.T130I与早发性和晚发性糖尿病相关，并导致HNF 4A表达下调，而HNF 1A多态性p.I27L和p.S487N与糖尿病诊断年龄相关。我们通过遗传和功能分析证明HNF 4A中的突变p.T130I是致病的，HNF 1A中预测的多态性p.I27L和p.S487N也是致病的。我们的研究结果表明，HNF 4A和HNF 1A基因突变可能是早发遗传性2型糖尿病的原因。
Maturity-onset diabetes of the young (MODY) is characterized by the onset of diabetes before the age of 25 years, positive family history, high genetic predisposition, monogenic mutations, and an autosomal dominant mode of inheritance. Here, we aimed to investigate the mutations and to characterize the phenotypes of a Han Chinese family with early-onset maternally inherited type 2 diabetes. Detailed clinical assessments and genetic screening for mutations in the HNF4α, GCK, HNF-1α, IPF-1, HNF1β, and NEUROD1 genes were carried out in this family. One HNF4A mutation (p.T130I) and two HNF1A polymorphisms (p.I27L and p.S487N) were identified. Mutation p.T130I was associated with both early-onset and late-onset diabetes and caused downregulated HNF4A expression, whereas HNF1A polymorphisms p.I27L and p.S487N were associated with the age of diagnosis of diabetes. We demonstrated that mutation p.T130I in HNF4A was pathogenic as were the predicted polymorphisms p.I27L and p.S487N in HNF1A by genetic and functional analysis. Our results show that mutations in HNF4A and HNF1A genes might account for this early-onset inherited type 2 diabetes.