University of Maryland School of Medicine, Department of Medicine, Baltimore, Maryland, USA.
Exeter Genomics Laboratory, Royal Devon and Exeter Hospital, Exeter, United Kingdom.
J Clin Invest. 2021 Feb 1;131(3). doi: 10.1172/JCI142244.
Monogenic diabetes refers to diabetes mellitus (DM) caused by a mutation in a single gene and accounts for approximately 1%-5% of diabetes. Correct diagnosis is clinically critical for certain types of monogenic diabetes, since the appropriate treatment is determined by the etiology of the disease (e.g., oral sulfonylurea treatment of HNF1A/HNF4A-diabetes vs. insulin injections in type 1 diabetes). However, achieving a correct diagnosis requires genetic testing, and the overlapping of the clinical features of monogenic diabetes with those of type 1 and type 2 diabetes has frequently led to misdiagnosis. Improvements in sequencing technology are increasing opportunities to diagnose monogenic diabetes, but challenges remain. In this Review, we describe the types of monogenic diabetes, including common and uncommon types of maturity-onset diabetes of the young, multiple causes of neonatal DM, and syndromic diabetes such as Wolfram syndrome and lipodystrophy. We also review methods of prioritizing patients undergoing genetic testing, and highlight existing challenges facing sequence data interpretation that can be addressed by forming collaborations of expertise and by pooling cases.
单基因糖尿病是指由单个基因突变引起的糖尿病（DM），约占糖尿病的 1%-5%。对于某些类型的单基因糖尿病，正确的诊断在临床上至关重要，因为疾病的病因决定了适当的治疗方法（例如，HNF1A/HNF4A-糖尿病用口服磺脲类药物治疗，1 型糖尿病则用胰岛素注射治疗）。然而，要做出正确的诊断需要进行基因检测，而单基因糖尿病的临床特征与 1 型和 2 型糖尿病的重叠，常常导致误诊。测序技术的改进增加了诊断单基因糖尿病的机会，但仍存在挑战。在这篇综述中，我们描述了单基因糖尿病的类型，包括常见和罕见的青年发病成年型糖尿病、新生儿糖尿病的多种病因以及沃勒姆综合征和脂肪营养不良等综合征性糖尿病。我们还回顾了对接受基因检测的患者进行优先排序的方法，并强调了目前在解释序列数据方面面临的挑战，这些挑战可以通过建立专业知识的合作和汇集病例来解决。
