摘要目的研究一个葡萄糖激酶（GCK）基因新发失活突变所致的青少年的成人起病型糖尿病（MODY）（GCK-MODY）家系的临床和遗传学特点。方法2015年12月，该家系的先证者为青年女性（31岁），体形正常（体质指数20.6 kg/m2），孕早期首次发现空腹血糖升高（7.3 mmol/L），伴糖化血红蛋白升高(6.6%)，血脂及超敏C反应蛋白等均正常，诊断为孕前糖尿病合并妊娠。先证者直系亲属中有三代糖尿病家族史，家系中其他糖尿病患者发病年龄40~55岁不等，主要依靠生活方式或二甲双胍干预。家族成员病程最长15年，目前无明显糖尿病并发症出现。对该家系患者进行外周血GCK基因测序及遗传学软件功能预测。通过人类基因突变数据进行比对。结果在该家系的所有患病个体中均发现GCK基因编码区10号外显子的缺失突变c.1289_1294 del TGACGC（p.lys 430fs），导致终止密码子的提前出现，并影响了下游剪接区的结构。文献复习发现GCK-MODY突变报道迄今已超过680种，主要表现为空腹血糖稳定升高（5.5~7.8 mmol/L），出生后持续终生，且不引起急慢性糖尿病并发症，往往仅在常规体检或孕期被诊断。除孕期外，治疗措施应以生活方式干预为宜。结论 GCK-MODY是一类以常染色体显性模式遗传的单基因疾病，孕早期为筛查该类疾病的敏感时期，一旦确诊应避免过度治疗。

abstractsObjective To explore the clinical and genetic features in a pedigree of maturity onset diabetes of the young (MODY) due to a novel glucokinase inactive mutation (GCK-MODY). Methods The clinical and genetic data of a dominantly inherited GCK-MODY family from Peking Union Medical College Hospital in December, 2015 were retrospectively analyzed. The proband was a 31-year-old female, who was found elevated fasting plasma glucose (7.3 mmol/L) during early pregnancy accompanied with increased glycated hemoglobin level (6.6%). The levels of serum lipid profiles and hypersensitive C reactive protein were normal. She was diagnosed with pregestational diabetes mellitus. The proband's immediate family members had three generations of diabetes history. The affected family members developed diabetes between 40 and 55 years old. Lifestyle intervention or metformin was the adopted treatments for hyperglycemia. Until now there were no obvious diabetes complications reported in this pedigree. The function of genetic variation was predicted by genetic function software and compared with Human Gene Mutuation Database. Results GCK gene sequencing showed all of the affected members had a novel heterozygotic deletion c.1289_1294 del TGACGC mutation(p.lys 430fs). Genetic function software suggested that this mutation led to not only splice site changes, but also premature termination codon. Literature review found there were above 680 kinds of GCK-MODY, which were dominantly inherited and had stable fasting hyperglycemia (5.5~7.8 mmol/L) without overt diabetes complication. Fasting hyperglycemia occurs in neonatal period but usually only can be found in medical check-up or during pregnancy. Therefore, it could be easily misdiagnosed as gestational diabetes mellitus. GCK-MODY rarely depends on pharmacotherapy except for during pregnancy and has a good prognosis. Conclusions GCK-MODY is a kind of monogenic diabetes with good prognosis and early pregnancy is a sensitive period for screening. Overtreatment should be avoided once the diagnosis is made.