University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford OX3 7LJ, UK.
Curr Opin Genet Dev. 2018 Jun;50:103-110. doi: 10.1016/j.gde.2018.04.006. Epub 2018 May 4.
Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic causes of beta-cell dysfunction and diabetes arising in children and young adults. Making an accurate diagnosis of MODY is important for establishing the correct management. Recent advances in our understanding of human sequence variation, through data collated in resources such as the Exome Aggregation Consortium have refined guidelines for assessment of rare genetic variants. This will allow a more precise aetiological diagnosis in childhood and young adult diabetes. No major new monogenic causes of diabetes outside the neonatal period have been identified in recent years, but the allelic spectrum of disease phenotype associated with known genes continues to expand. Improving uptake of genetic testing by defining who should be tested is an area of active research. A population based study found that 6.5% of children who have negative beta-cell antibodies at diagnosis have rare functional variants in MODY genes. Defining the high risk groups in adults with diabetes is more difficult, but online decision aids will assist clinicians in selecting who to refer for testing.
青少年起病的成年型糖尿病（MODY）是一组由儿童和青年时期发生的β细胞功能障碍和糖尿病的单基因病因引起的异质性疾病。对 MODY 做出准确的诊断对于确立正确的治疗方案非常重要。通过 Exome Aggregation Consortium 等资源中收集的数据，我们对人类序列变异的理解不断深入，从而对罕见遗传变异的评估指南进行了修订。这将使得在儿童和青年期糖尿病中进行更精确的病因诊断成为可能。近年来，除新生儿期外，尚未发现任何新的主要的糖尿病单基因病因，但与已知基因相关的疾病表型等位基因谱仍在不断扩大。通过明确应该进行基因检测的人群，提高基因检测的接受程度是目前研究的重点。一项基于人群的研究发现，在诊断时β细胞抗体阴性的儿童中，有 6.5%存在 MODY 基因的罕见功能变异。在糖尿病成人中确定高危人群更为困难，但在线决策辅助工具将有助于临床医生选择需要进行检测的患者。
