First Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
Oku Medical Clinic, Wakayama, Japan.
J Diabetes Investig. 2020 Mar;11(2):333-336. doi: 10.1111/jdi.13138. Epub 2019 Sep 19.
Activating mutations in the ABCC8 gene cause diabetes and inactivating mutations usually cause hyperinsulinemic hypoglycemia in infancy. Patients with hypoglycemia in infancy due to a heterozygous inactivating mutation have been reported to occasionally progress to diabetes later in life. We explored the gene responsible for diabetes in two brothers, who were suspected to have diabetes at 15 and 18 years-of-age, respectively, with whole exome sequencing, and identified a compound heterozygous ABCC8 gene mutation (p.Arg168Cys and p.Arg1421Cys). Although their father and mother were heterozygous carriers of the p.Arg168Cys and the p.Arg1421Cys mutation, respectively, neither parent had diabetes. These mutations have been reported to be responsible for hypoglycemia in infancy and function as an inactivating mutation. Our results suggest that the inactivating ABCC8 gene mutation is also important in the etiology of diabetes.
ABCC8 基因突变可导致糖尿病，而失活突变通常会导致婴儿时期的高胰岛素血症性低血糖。有报道称，患有婴儿期低血糖症的杂合失活突变患者在以后的生活中偶尔会发展为糖尿病。我们通过外显子组测序，对两名分别在 15 岁和 18 岁时被怀疑患有糖尿病的兄弟进行了研究，发现了一种 ABCC8 基因突变的复合杂合性（p.Arg168Cys 和 p.Arg1421Cys）。尽管他们的父亲和母亲分别为 p.Arg168Cys 和 p.Arg1421Cys 突变的杂合子携带者，但他们的父母均没有糖尿病。这些突变被报道与婴儿期低血糖有关，并且起失活突变的作用。我们的研究结果表明，失活的 ABCC8 基因突变也与糖尿病的病因有关。
