葡萄糖激酶新发基因突变致MODY2一家系的临床及分子遗传学分析  

Clinical and molecular genetic analysis of one MODY2 family caused by novel glucokinase gene mutation

作　　者：郑婷娟 张同 王玉环[1] ZHENG Tingjuan;ZHANG Tong;WANG Yuhuan(Department of Endocrinology,The Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004,China)

机构地区：[1]西安交通大学第二附属医院内分泌科,陕西西安710004

出　　处：《西安交通大学学报（医学版）》2024年第6期1032-1036,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：西安交通大学第二附属医院科研基金自由探索项目[No.2020YJ(ZYTS)273]。

摘　　要：目的报道1例中国人葡萄糖激酶(glucokinase,GCK)新发基因突变导致青少年起病的成人型糖尿病2型(maturity-onset diabetes of the young,type 2,MODY2)家系,分析其遗传学特征及临床特点。方法对1例MODY2家系行基因测序、临床资料采集及分析。结果调查此家系成员共18人,其中先证者及其弟、父亲、叔父、堂弟等父系成员11人罹患糖尿病;先证者及其弟、父亲、叔父均存在GCK基因杂合同义突变(exon1:c.45G>A:p.K15K),生物信息学功能预测提示该突变可能影响mRNA剪接而致GCK功能受损,国内研究人群尚未见此突变报道;先证者及其弟糖化血红蛋白分别为6.49%、6.72%,空腹血糖分别为6.80、7.01 mmol/L,糖尿病自身抗体谱均为阴性,6~18个月随访示血糖水平保持稳定。结论此MODY2家系中GCK基因杂合同义突变(exon1:c.45G>A:p.K15K)为中国人新发突变位点,其临床表现为轻度、持续稳定的空腹高血糖及糖化血红蛋白升高,不应低估GCK基因同义突变的致病性。Objective To report a Chinese family with maturity-onset diabetes of the young,type 2(MODY2)caused by a novel glucokinase(GCK)gene mutation and to analyze its genetic and clinical characteristics.Methods Gene sequencing,clinical data collection and analysis were performed on a MODY2 family.Results A total of 18 members of this family were investigated,of whom 11 were diabetic,including the proband and her younger brother,father,uncle,cousin and other paternal members.The proband and her brother,father and uncle all had heterosense mutations of GCK gene(exon1:c.45G>A:p.K15K).Bioinformatics function prediction suggested that the mutation might affect mRNA splicing and lead to impaired GCK function.The mutation has not been reported in research on domestic population.The glycosylated hemoglobin levels of the proband and her younger brother were 6.49%and 6.72%;their fasting blood glucose levels were 6.80 mmol/L and 7.01 mmol/L,respectively.The diabetes autoantibody profiles were negative.Blood glucose levels remained stable during 6-18 months of follow-up.Conclusion The heterosense mutation of GCK gene in the MODY-2 family(exon1:c.45G>A:p.K15K)is a newly discovered mutation site in the Chinese population,and its clinical manifestations are mild,persistent and stable fasting hyperglycemia,and elevated glycosylated hemoglobin.The pathogenicity of GCK gene synonymous mutations should not be underestimated.

关 键 词：青少年起病的成人型糖尿病(MODY) 葡萄糖激酶(GCK) 基因突变 

分 类 号：R587.1[医药卫生—内分泌]