四例中国青少年的成人起病型糖尿病2型家系的临床与分子遗传学研究

目的探讨中国青少年的成人起病型糖尿病2型（MODY2）患者的临床特点和分子遗传学特征。方法对2013年2月至8月北京协和医院诊断的4例MODY2家系患者的临床特点及实验室检查资料进行系统性分析并抽提相关家系成员的基因组DNA，聚合酶链式反应（PCR）扩增后进行葡萄糖激酶（GCK）基因直接测序。结果在4例家系中共诊断10例GCK基因突变引起的糖尿病和糖调节受损患者。在8例有临床资料的患者中，高血糖的诊断年龄为5．3～44．0岁，查体是主要发现形式，所有患者血甘油三酯水平均正常或低于正常下限。4个家系的GCK基因检测发现2个新突变c．749G〉A（R250H）和C．781G〉C（G261R）和2个已报突变e．127C〉T（R43C）和c．571C〉T（R191W）。结论中国MODY2患者临床表现多样，GCK基因C．749G〉A突变可能是MODY2的致病原因。

Clinical characteristics and molecular genetics in four Chinese pedigrees of maturity-onset diabetes ofthe young type 2

Objective To investigate the clinical characteristics, cause of disease on Chinese maturity-onset diabetes of the young type 2 （ MODY2 ）. Methods Four Chinese pedigrees of MODY2 diagnosed by Peking Union Medical College Hospital from February to August in 2013 were analyzed for their clinical features and laboratory data. Genomic DNA of related members in the pedigrees were extracted, followed by amplification with polymerase chain reaction. Then direct sequencing were performed to identify mutations in glucokinase （GCK） gene. Results Totally 10 cases of diabetes and impaired glucose regulation （IGR） caused by GCK mutations were diagnosed in four pedigrees. Age at diagnosis for hyperglycemia was between 5.3 and 44. 0 years. Health examination was the most common way to find hyperglycemia. All cases＇ plasma triglyceride were in the normal range or below the lower linfit. Genetic testing for GCK gene found four mutations, two new heterozygous mutation c. 749G 〉 A （ R250H ） and c. 781G 〉 C（G261R）, two previously reported mutation c. 127C 〉 T（R43C） and c. 571C 〉 T（R191W）. Conclusion Clinical manifestations are various in Chinese MODY2 patients. GCK gene c. 749G 〉 A mutation may be the cause of MODY2.