Sarmadi Akram, Mohammadi Aliasgar, Tabatabaei Fatemeh, Nouri Zahra, Chaleshtori Morteza Hashemzadeh, Tabatabaiefar Mohammad Amin
Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Adv Biomed Res. 2020 Jun 27;9:25. doi: 10.4103/abr.abr_18_20. eCollection 2020.
Diabetes mellitus (DM) is a group of metabolic disorders in the body, accompanied with increasing blood sugar levels. Diabetes is classified into three groups: Type 1 DM (T1DM), Type 2 DM (T2DM), and monogenic diabetes. Maturity-onset diabetes of the young (MODY) is a monogenic diabetes that is frequently mistaken for T1D or T2D. The aim of this study was to diagnose MODY and its subtype frequency in a diabetic population in Iran.
In this study among ten diabetic families that were highly suspected to MODY by nongenetic biomarkers and without any pathogenic mutation in and genes, two patients from two unrelated families were examined via whole-exome sequencing (WES) in order to detect the causative gene of diabetes. Co-segregation analysis of the identified variant was performed using Sanger sequencing.
In this study, no pathogenic variant was found in and genes (MODY2 and MODY3), while these two types of MODY were introduced as the most frequent in other studies. By using WES, a pathogenic variant (p.I488T) was found in one of the patients in gene causing MODY8 that its frequency is very rare in other studied populations. A high-risk variant associated with diabetes was found in another patient.
WES was applied in this study to reveal the cause of MODY in 1 family. This pathogenic mutation was previously reported as a disease causing mutation.
糖尿病（DM）是一组体内代谢紊乱疾病，伴有血糖水平升高。糖尿病分为三组：1型糖尿病（T1DM）、2型糖尿病（T2DM）和单基因糖尿病。青年发病的成年型糖尿病（MODY）是一种单基因糖尿病，常被误诊为T1D或T2D。本研究的目的是诊断伊朗糖尿病患者群体中的MODY及其亚型频率。
在本研究中，对10个通过非遗传生物标志物高度怀疑患有MODY且在 和 基因中无任何致病突变的糖尿病家族，选取来自两个无关家族的两名患者进行全外显子组测序（WES），以检测糖尿病的致病基因。使用桑格测序法对鉴定出的变异进行共分离分析。
在本研究中，在 和 基因（MODY2和MODY3）中未发现致病变异，而在其他研究中这两种类型的MODY被认为是最常见的。通过WES，在一名患者的 基因中发现了一个致病变异（p.I488T），该变异导致MODY8，其频率在其他研究人群中非常罕见。在另一名患者中发现了一个与糖尿病相关的高风险变异。
本研究应用WES揭示了1个家族中MODY的病因。这种致病突变先前已被报道为致病突变。
