Update of variants identified in the pancreatic β-cell KATP channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes
Update of variants identified in the pancreatic β-cell KATP channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes
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DOI：
10.1002/humu.23995
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发表时间：
2020-02-17
期刊：
影响因子：
3.9
通讯作者：
Flanagan, Sarah E.
中科院分区：
文献类型：
--
作者：
De Franco, Elisa;Saint-Martin, Cecile;Flanagan, Sarah E.
新生儿糖尿病和高胰岛素血症最常见的遗传原因是ABCC 8和KCNJ 11的致病性变体。这些基因编码β细胞ATP敏感钾通道的亚基，这是葡萄糖刺激胰岛素分泌途径的关键组成部分。这两个基因的突变导致胰岛素分泌失调;失活突变导致胰岛素分泌过多，导致先天性高胰岛素血症，而激活突变导致相反的表型，糖尿病。本文综述了ABCC 8和KCNJ 11中发现的变异，表型谱和对致病变异个体的治疗意义。
The most common genetic cause of neonatal diabetes and hyperinsulinism is pathogenic variants in ABCC8 and KCNJ11. These genes encode the subunits of the beta-cell ATP-sensitive potassium channel, a key component of the glucose-stimulated insulin secretion pathway. Mutations in the two genes cause dysregulated insulin secretion; inactivating mutations cause an oversecretion of insulin, leading to congenital hyperinsulinism, whereas activating mutations cause the opposing phenotype, diabetes. This review focuses on variants identified in ABCC8 and KCNJ11, the phenotypic spectrum and the treatment implications for individuals with pathogenic variants.