Congenital hyperinsulinism: Clinical and molecular analysis of a large Italian cohort
Congenital hyperinsulinism: Clinical and molecular analysis of a large Italian cohort
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DOI：
10.1016/j.gene.2013.03.021
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发表时间：
2013-05-25
期刊：
影响因子：
3.5
通讯作者：
Gasparini, Paolo
中科院分区：
文献类型：
--
作者：
Faletra, Flavio;Athanasakis, Emmanouil;Gasparini, Paolo
先天性高胰岛素血症（CHI）是一种遗传性疾病，其特征是与不适当的胰岛素分泌有关的严重低血糖。它是一种异质性疾病，可分为两大类：一类是由于atp敏感钾通道缺陷引起的“通道病”，由ABCC8和KCNJ11基因编码；另一类是由几种基因（GLUD1、GCK、HADH、SLC16A1、HNF4A和HNF1A）突变引起的“代谢病”，涉及不同的代谢途径。为了阐明意大利人群CHI的遗传病因，我们对36例患者进行了CHI相关基因的广泛测序分析：29例患有经典高胰岛素血症（HI）， 7例患有高胰岛素血症-高氨血症（HI/HA）。在15例HI患者中发现17个突变，在5例HI/HA患者中发现5个突变。我们的数据证实了atp敏感钾通道在意大利病例发病机制中的主要作用（类似于70%），而其余百分比应归因于其他因素。更好地了解CHI的分子基础将有助于改进遗传筛查和产前诊断策略。此外，遗传分析也可能有助于区分CHI的两种组织病理学形式，这将导致治疗和遗传咨询的明显改善。(C) 2013 Elsevier B.V.版权所有
Congenital hyperinsulinism (CHI) is a genetic disorder characterized by profound hypoglycemia related to an inappropriate insulin secretion. It is a heterogeneous disease classified into two major subgroups: "channelopathies" due to defects in ATP-sensitive potassium channel, encoded by ABCC8 and KCNJ11 genes, and "metabolopathies" caused by mutation of several genes (GLUD1, GCK, HADH, SLC16A1, HNF4A and HNF1A) and involved in different metabolic pathways. To elucidate the genetic etiology of CHI in the Italian population, we conducted an extensive sequencing analysis of the CHI-related genes in a large cohort of 36 patients: Twenty-nine suffering from classic hyperinsulinism (HI) and seven from hyperinsulinism-hyperammonemia (HI/HA). Seventeen mutations have been found in fifteen HI patients and five mutations in five HI/HA patients. Our data confirm the major role of ATP-sensitive potassium channel in the pathogenesis of Italian cases (similar to 70%) while the remaining percentage should be attributed to other. A better knowledge of molecular basis of CHI would lead to improve strategies for genetic screening and prenatal diagnosis. Moreover, genetic analysis might also help to distinguish the two histopathological forms of CHI, which would lead to a clear improvement in the treatment and in genetic counseling. (C) 2013 Elsevier B.V. All rights reserved.