Pace Nikolai Paul, Rizzo Christopher, Abela Alexia, Gruppetta Mark, Fava Stephen, Felice Alex, Vassallo Josanne
Centre for Molecular Medicine and Biobanking, University of Malta, Msida, Malta.
Department of Medicine, Mater Dei Hospital, Msida, Malta.
Clin Med Insights Case Rep. 2019 Feb 20;12:1179547619831034. doi: 10.1177/1179547619831034. eCollection 2019.
The diagnosis of maturity onset diabetes of the young (MODY) is a challenging process in view of the extensive clinical and genetic heterogeneity of the disease. Mutations in the gene encoding hepatocyte nuclear factor 1α () are responsible for most forms of monogenic diabetes in Northern European populations. Genetic analysis through a combination of whole exome sequencing and Sanger sequencing in three Maltese siblings and their father identified a rare duplication/frameshift mutation in exon 4 of that lies within a known mutational hotspot in this gene. In this report, we provide the first description of an -MODY3 phenotype in a Maltese family. The findings reported are relevant and new to a regional population, where the epidemiology of atypical diabetes has never been studied before. This report is of clinical interest as it highlights how monogenic diabetes can be misdiagnosed as either type 1, type 2, or gestational diabetes. It also reinforces the need for a better characterisation of monogenic diabetes in Mediterranean countries, particularly in island populations such as Malta with a high prevalence of diabetes.
鉴于青年发病的成年型糖尿病（MODY）具有广泛的临床和遗传异质性，其诊断过程颇具挑战性。在北欧人群中，编码肝细胞核因子1α（HNF1α）的基因突变是导致大多数单基因糖尿病的原因。通过对三名马耳他同胞及其父亲进行全外显子组测序和桑格测序相结合的遗传分析，在HNF1α基因第4外显子中发现了一个罕见的重复/移码突变，该突变位于该基因已知的突变热点区域内。在本报告中，我们首次描述了一个马耳他家族中的HNF1α-MODY3表型。报告中的发现对于一个此前从未研究过非典型糖尿病流行病学的地区人群而言具有相关性和新颖性。本报告具有临床意义，因为它突出了单基因糖尿病如何可能被误诊为1型、2型或妊娠期糖尿病。它还强化了在地中海国家更好地描述单基因糖尿病的必要性，特别是在糖尿病患病率较高的岛屿人群如马耳他。
