中国青少年的成人起病型糖尿病1型一例家系研究

A pedigree research of maturity onset diabetes of the young type 1 in China

目的探讨中国青少年的成人起病型糖尿病1型（MODY1）患者的临床特点和分子遗传学特征。方法对北京协和医院于2015年8月诊断的1例MODY患者家系的临床特征、实验室资料进行分析，运用Sanger测序技术对先证者及相关家系成员进行肝细胞核因子（HNF）1α基因、HNF4α基因、葡萄糖激酶（GCK）基因测序。结果在该家系的2名家系成员（先证者及其母亲）中检测到HNF4α基因（NM_000457．4）第8号外显子c．992G〉A（p．R331H）杂合突变。对基因诊断明确为MODY1型的先证者进行小剂量磺脲类药物替代胰岛素转换治疗，患者血糖控制更加平稳。结论中国人群中存在HNF4α基因突变导致的MODY1型家系。MODY可能与2型糖尿病混合存在于同一家系内，容易被误诊，需要引起重视。

Objective To investigate the clinical and genetic characteristics of a Chinese pedigree with maturity onset diabetes of the young type I（MODY 1）. Methods A Chinese pedigree of MODY diagnosed in Peking Union Medical College Hospital in August 2015 was analyzed for the clinical features and laboratory data. Genomic DNA of related members in the pedigree were extracted. And Sanger sequencing was performed to identify mutations in hepatoeyte nuclear factor （HNF）1α gene, HNF4α gene and glucokinase （GCK） gene in this pedigree. Results A heterozygous mutation in HNF4α gene （NM_ 000457.4） located in the exon 8 （c.992G〉A; p.R331H） was identified in two members of the pedigree（the proband and his mother）. After the genetic diagnosis of the MODY 1, the proband was given a small dose of sulfonylurea instead of insulin for glucose-lowering therapy. As a result, the proband got a much more stable blood glucose. Conclusions There are MODY 1 pedigrees caused by HNF4α gene heterozygous mutations in Chinese population. A correct genetic diagnosis can significantly improve the treatment and blood control of the patients. MODY may co-exist with type 2 diabetes in a same pedigree, which is tend to be misdiagnosed, and should be paid more attention.