两例GCK基因突变家系的分子遗传学分析及临床思考

Molecular genetic analysis and clinical consideration of two families with GCK gene mutation

目的探讨2例葡萄糖激酶基因(GCK,NM_000162.4、NP_000153.1)突变导致的青少年的成人发病型糖尿病(MODY)患者的分子遗传学及临床特征。方法收集2015年4月至2015年12月北京积水潭医院收治并疑诊为MODY的2例患者的临床资料并进行分析,对该2例患者及其家系成员进行GCK基因测序,分析致病原因。结果在2例家系中,发现1个新的GCK基因杂合突变p.T82P(c.244 A>C)和1个已报告的GCK基因杂合突变p.V412M(c.1234G>A)。在临床表现方面,在2个家系的3例GCK基因突变携带者中,除血糖升高外,尚有不同程度的代谢综合征的临床表现。结论GCK基因T82P突变可能是MODY2的致病原因。GCK基因突变携带者临床表现复杂,在治疗和预后判断上需要个体化。

Objective To explore the molecular genetics and clinical characteristics of two cases of maturity-onset diabetes of the young(MODY)type 2 caused by glucokinase(GCK)gene mutation.Methods Two patients who were admitted into Beijing Jishuitan Hospital with suspected diagnosis of MODY from April 2015 to December 2015 were collected and analyzed by their clinical data.GCK gene sequencing was carried out for the two patients and their family members to find the cause of their disease.Results A new GCK heterozygous mutation p.T82P(c.244 A>C)and a reported GCK heterozygous mutation p.V412M(c.1234 G>A)were found in the two families.In the aspect of clinical manifestations,in addition to stable hyperglycemia,the 3 GCK gene mutation carriers in the two families showed metabolic syndrome of varying degrees.Conclusions GCK gene mutation p.T82P may be the cause of MODY2.The clinical manifestations of GCK gene mutation carriers are complex,and they need to be individualized and managed in treatment and prognosis.