Open Access中国早发糖尿病患者ABCC8基因变异的临床特征分析
Author(s) -
Li Meng,
Gong Siqian,
Han Xueyao,
Zhang Simin,
Ren Qian,
Cai Xiaoling,
Luo Yingying,
Zhou Lingli,
Zhang Rui,
Liu Wei,
Zhu Yu,
Zhou Xianghai,
Sun Yanfang,
Li Yufeng,
MA Yumin,
Ji Lig
Publication year - 2021
Publication title -
journal of diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.949
H-Index - 43
eISSN - 1753-0407
pISSN - 1753-0393
DOI - 10.1111/1753-0407.13144
Subject(s) - hyperinsulinemic hypoglycemia , medicine , maturity onset diabetes of the young , missense mutation , diabetes mellitus , molecular genetics , genetic heterogeneity , hypoglycemia , bioinformatics , genetics , type 2 diabetes , phenotype , endocrinology , biology , gene
Background ABCC8 variants cause neonatal diabetes, maturity onset diabetes of the young (MODY), and hyperinsulinemic hypoglycemia because of activating or inactivating variants. In this study we used targeted exon sequencing to investigate genetic variants of ABCC8 and phenotypic features in Chinese patients with early onset diabetes (EOD). Methods A cross‐sectional study of 543 Chinese patients with EOD was recruited and the exons of them were conducted targeted sequencing. The pathogenicity of ABCC8 variants was defined according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guideline. The phenotypes of patients owing to ABCC8 variants ( ABCC8‐ MODY) were characterized. Results Among the 543 participants, eight (1.5%) patients with ABCC8‐ MODY were identified. They harbored eight missense ABCC8 variants (p.R306C, p.E1326K, and p.R1379H, previously reported; p.R298C, p.F1176C, p.R1221W, p.K1358R, and p.I1404V) classified as likely pathogenic. Two family members with ABCC8 ‐MODY were also confirmed. The average diagnosed age of the 10 patients was 26.8 ± 12.9 years. The majority of them had unsatisfactory glucose control, 80% of them had diabetic kidney disease, and neurological features were not observed. Conclusion Using targeted exon sequencing followed by pathogenicity analysis, we could be able to make genetic diagnoses for eight (1.5%) patients with ABCC8‐ MODY. The phenotype was variable with higher risk of diabetic microvascular complications. Genetic diagnosis is conducive for facilitating the personalized treatment of ABCC8 ‐MODY.