Molecular Genetic Study in a Cohort of Iranian Families Suspected to Maturity-Onset Diabetes of the Young, Reveals a Recurrent Mutation and a High-Risk Variant in the CEL Gene

Akram Sarmadi; Aliasgar Mohammadi; Fatemeh Tabatabaei; Zahra Nouri; Morteza Hashemzadeh Chaleshtori; Mohammad Amin Tabatabaiefar

doi:10.4103/abr.abr_18_20

Molecular Genetic Study in a Cohort of Iranian Families Suspected to Maturity-Onset Diabetes of the Young, Reveals a Recurrent Mutation and a High-Risk Variant in the CEL Gene

Adv Biomed Res. 2020 Jun 27:9:25. doi: 10.4103/abr.abr_18_20. eCollection 2020.

Authors

Akram Sarmadi¹, Aliasgar Mohammadi², Fatemeh Tabatabaei³, Zahra Nouri⁴, Morteza Hashemzadeh Chaleshtori¹, Mohammad Amin Tabatabaiefar^{2

5}

Affiliations

¹ Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
² Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
³ Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Science, Isfahan, Iran.
⁴ Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
⁵ Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.

Abstract

Background: 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.

Materials and methods: In this study among ten diabetic families that were highly suspected to MODY by nongenetic biomarkers and without any pathogenic mutation in GCK and HNF1A 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.

Results: In this study, no pathogenic variant was found in GCK and HNF1A 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 CEL 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.

Conclusion: 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.

Keywords: Carboxyl ester lipase; maturity-onset diabetes of the young; pathogenic variant; whole-exome sequencing.