Study of the frequency and clinical features of maturity-onset diabetes in the young in the pediatric and adolescent diabetes population in Iran

Abstract

Objectives Maturity-onset diabetes of the young (MODY), an autosomal dominant disease, is frequently misdiagnosed as type 1 or 2 diabetes. Molecular diagnosis is essential to distinguish them. This study was done to investigate the prevalence of MODY subtypes and patients’ clinical characteristics. Methods A total of 43 out of 230 individuals with diabetes were selected based on the age of diagnosis >6 months, family history of diabetes, absence of marked obesity, and measurable C-peptide. Next-generation and direct SANGER sequencing was performed to screen MODY-related mutations. The variants were interpreted using the Genome Aggregation Database (genomAD), Clinical Variation (ClinVar), and pathogenicity prediction tools. Results There were 23 males (53.5%), and the mean age at diabetes diagnosis was 6.7 ± 3.6 years. Sixteen heterozygote single nucleotide variations (SNVs) from 14 patients (14/230, 6%) were detected, frequently GCK (37.5%) and BLK (18.7%). Two novel variants were identified in HNF4A and ABCC8. Half of the detected variants were categorized as likely pathogenic. Most prediction tools predicted Ser28Cys in HNF4A as benign and Tyr123Phe in ABCC8 as a pathogenic SNV. Six cases (42.8%) with positive MODY SNVs had islet autoantibodies. At diagnosis, age, HbA1C, and C-peptide level were similar between SNV-positive and negative patients. Conclusions This is the first study investigating 14 variants of MODY in Iran. The results recommend genetic screening for MODY in individuals with unusual type 1 or 2 diabetes even without family history. Treatment modifies depending on the type of patients’ MODY and is associated with the quality of life.

From Genes to Diagnosis: Examining the Clinical and Genetic Spectrum of Maturity-Onset Diabetes of the Young (MODY) in TCGS

“…Mentioned Kuwaiti study and other studies in Iran, rstly chose phenotypically possible MODY cases for detecting causal variants. This is while the reported variants may have a high allele frequency when evaluating the whole population genetic spectrum, which makes them unlikely to be causative for a monogenic rare disease [5,[47][48][49]. Also, as some MODY subtypes like GCK-MODY2 mostly show mild hyperglycemia which is sometimes even undetectable, an exclusive clinical approach to select samples based on phenotype for nding causative mutation seems inadequate.…”