5个葡萄糖激酶基因突变家系的临床特征与遗传分析  

Clinical characterization and genetic analysis of 5 Chinese families with glucokinase gene mutations

作　　者：陈远思 邵明玮[1] 任高飞[1] 陈铎[2] 郭丰[1] 刘艳霞[1] 李志臻[1] 孙良阁[1] 秦贵军[1] Chen Yuansi;Shao Mingwei;Ren Gaofei;Chen Duo;Guo Feng;Liu Yanxia;Li Zhizhen;Sun Liangge;Qin Guijun(Department of Endocrinology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Genetics and Prenatal Diagnosis Center,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院内分泌科,450052 [2]郑州大学第一附属医院遗传与产前诊断中心,450052

出　　处：《中华内分泌代谢杂志》2022年第8期645-650,共6页Chinese Journal of Endocrinology and Metabolism

摘　　要：目的报道并总结5个葡萄糖激酶(GCK)基因突变导致的青少年成人起病型糖尿病2型(MODY2)家系临床表现和分子遗传学特征。方法收集先证者临床资料和生化检查。采集先证者及一级家属外周血,采用二代测序法进行全外显子组基因检测。与数据库对比筛选可疑致病位点进行Sanger测序验证。结果5位先证者均表现出轻度空腹高血糖,HbA1C<7.5%,无口渴、多饮、多尿症状。5个家系中存在6个突变位点,其中M1:c.555delT(p.Leu186Cysfs Ter19)和M3:c.263T>A(p.Met88Lys)未见文献报道。随访过程中,5位先证者除2位妊娠女性建议根据胎儿基因型,必要时应用胰岛素治疗外,余均行生活方式干预。结论在符合MODY诊断标准的患者中,对于轻度高血糖、家族史明确的儿童或妊娠期女性应进行MODY2筛查,GCK基因检测是诊断金标准,精准诊断将有利于选择更合适的治疗方案。Objective To summarize the clinical manifestations and molecular genetic characteristics of 5 families with maturity-onset diabetes mellitus of the young 2(MODY2)caused by glucokinase(GCK)gene mutations.Methods Clinical data and biochemical results of probands were collected.Peripheral blood samples of probands and first-degree family members were collected and whole exome gene was detected using second-generation sequencing.After comparing against the database,the suspected pathogenic sites were selected for Sanger sequencing verification.Results All the 5 probands presented with mild fasting hyperglycemia,HbA1C<7.5%,and no symptoms of thirst,polydipsia or polyuria.There were 6 mutants in 5 families,including M1:c.555delT(P.leu186CysFS Ter19)and M3:c.263T>A(p.Met88Lys)which haven′t been reported before.During the follow-up,all probands received life-style intervention,except 2 pregnant women who should consider insulin treatment if necessary according to fetal genotypes.Conclusion Among patients who meet the diagnostic criteria for MODY,MODY2 screening should be performed for children or pregnant women with mild hyperglycemia and family history.GCK gene detection is the gold standard for diagnosis,and accurate diagnosis will be conducive to the selection of appropriate treatment.

关 键 词：葡萄糖激酶基因 青少年的成人起病型糖尿病2型 空腹高血糖 基因突变 

分 类 号：R587.1[医药卫生—内分泌] R440[医药卫生—内科学]