Monogenic Forms of Diabetes Mellitus.
Monogenic Forms of Diabetes Mellitus.
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DOI：
10.1007/978-3-030-25905-1_18
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发表时间：
2019-01-01
影响因子：
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通讯作者：
Balogh, Istvan
中科院分区：
文献类型：
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作者：
Gaal, Zsolt;Balogh, Istvan
除了常见类型的糖尿病之外，还存在两种主要的单基因糖尿病形式。青年成熟型糖尿病（MODY）是一组单基因常染色体显性遗传疾病。MODY占所有糖尿病病例的1-2%，它不仅诊断不足，而且经常被误诊为1型或2型糖尿病。目前已鉴定的MODY基因有十几个，其分子分类对于正确的治疗决策和预后判断具有重要意义。最常见的亚型是HNF 1A、GCK和HNF 4A。MODY的基因检测最近由于技术进步而发生了变化，与过去进行的顺序检测相反，现在所有MODY基因都可以通过下一代测序同时进行检测。单基因糖尿病的另一个主要类别是新生儿糖尿病，它可以是短暂的或永久的，并且通常糖尿病是综合征的一部分。它是一种严重的单基因疾病，出现在出生后的前6个月。高血糖通常需要胰岛素。新生儿糖尿病分为永久性和短暂性两种。在TNDM中，糖尿病通常在几个月内恢复，但可能在以后的生活中复发。NDM的发病率为1：100，000 -1：400，000活产，PNDM占病例的一半。最常见的是，新生儿糖尿病是由编码β细胞ATP依赖性钾通道的KCNJ 11和ABCC 8基因突变引起的。自从发现新生儿糖尿病的分子背景以来，新生儿糖尿病已经快速而成功地过渡到临床实践中。对于这两种遗传性糖尿病，最近的指南建议进行基因检测。
In addition to the common types of diabetes mellitus, two major monogenic diabetes forms exist. Maturity-onset diabetes of the young (MODY) represents a heterogenous group of monogenic, autosomal dominant diseases. MODY accounts for 1-2% of all diabetes cases, and it is not just underdiagnosed but often misdiagnosed to type 1 or type 2 diabetes. More than a dozen MODY genes have been identified to date, and their molecular classification is of great importance in the correct treatment decision and in the judgment of the prognosis. The most prevalent subtypes are HNF1A, GCK, and HNF4A. Genetic testing for MODY has changed recently due to the technological advancements, as contrary to the sequential testing performed in the past, nowadays all MODY genes can be tested simultaneously by next-generation sequencing. The other major group of monogenic diabetes is neonatal diabetes mellitus which can be transient or permanent, and often the diabetes is a part of a syndrome. It is a severe monogenic disease appearing in the first 6months of life. The hyperglycemia usually requires insulin. There are two forms, permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). In TNDM, the diabetes usually reverts within several months but might relapse later in life. The incidence of NDM is 1:100,000-1:400,000 live births, and PNDM accounts for half of the cases. Most commonly, neonatal diabetes is caused by mutations in KCNJ11 and ABCC8 genes encoding the ATP-dependent potassium channel of the beta cell. Neonatal diabetes has experienced a quick and successful transition into the clinical practice since the discovery of the molecular background. In case of both genetic diabetes groups, recent guidelines recommend genetic testing.