Screening and clinical characteristics of mutations in ABCC8 gene in pedigrees of maturity-onset diabetes of the young
10.3969/j.issn.1006-6187.2025.08.008
- VernacularTitle:青少年起病的成人型糖尿病家系ABCC8基因突变筛查与临床特点的研究
- Author:
Tiantian LI
1
;
Yanyan JIANG
;
Xiaoxu GE
;
Ming LI
;
Chanwei LIU
;
Rong ZHANG
;
Yating CHEN
;
Fusong JIANG
;
Limei LIU
Author Information
1. 200233 上海交通大学医学院附属第六人民医院内分泌代谢科
- Publication Type:Journal Article
- Keywords:
Maturity-onset diabetes of the young;
ABCC8 gene;
Maturity-onset diabetes of young 12;
D655V mutation;
R825Q mutation
- From:
Chinese Journal of Diabetes
2025;33(8):597-604
- CountryChina
- Language:Chinese
-
Abstract:
Objective To screen the mutations of ABCC8 gene in probands of maturity-onset diabetes of the young pedigrees,and investigate it sgenetic and clinical characteristics.Methods Whole exome sequencing were performed to screen ABCC8 mutations in 56 MODY probands who were admitted to Department of Endocrinology and Metabolism,Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2021 to December 2023.The mutations were verified by Sanger sequencing,and all participants were genotyped.Clinical phenotypes of the mutation carriers were compared with non-DM controls within the families.The identified mutations were evaluated by bioinformatic softwires.Then the pharmacogenomic characteristics of the mutation carriers were analyzed.Results Two heterozygous mutations D655V and R825Q were identified in two MODY probands and their families respectively,and the D655V was a novel mutation.Bioinformatics studies showed that both mutations were deleterious and pathogenic.In comparison with non-DM controls in the two families,mutation carriers with diabetes exhibited significantly lower fasting insulin/fasting plasma glucose,two-hour postprandial insulin/two-hour postprandial insulin plasma glucose,homeostatic model assessment-β(P<0.05).Treatment with oral hypoglycemic agents such as metformin or insulin in these mutation carriers resulted in a moderate reduction in plasma glucose levels.However,switching to targeted Sulfonylurea's(SUs)proved to be more effective.Conclusions In this study,the prevalence of MODY12 is 3.6%in these MODY pedigrees.The remarkable hypoglycemic efficacy of SUs suggests that both D655V and R825Q were activating mutations of ABCC8,and maybe the cause of MODY12 characterized by impaired insulin secretion.
