Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share By
Investigating Genetic Mutations in a Large Cohort of Iranian Patients With Congenital Hyperinsulinism Publisher Pubmed



Razzaghyazar M1, 2 ; Saeedi S1, 3 ; Dayani SB1 ; Enayati S1 ; Abbasi F4 ; Hashemian S5 ; Eshraghi P5 ; Karimdadi S5 ; Tajdini P4 ; Vakili R5 ; Amoli MM1 ; Yaghootkar H6, 7, 8
Authors

Source: JCRPE Journal of Clinical Research in Pediatric Endocrinology Published:2022


Abstract

Objective: Congenital hyperinsulinism (CHI) is the most frequent cause of severe and persistent hypoglycaemia from birth. Understanding the pathophysiology and genetic defects behind hyperinsulinism and its complications provides clues to timely diagnosis and management. The aim of this study was to evaluate the underlying genetic aetiology of a specific Iranian pediatric cohort with CHI. Methods: A total of 44 unrelated children, 20 girls and 24 boys, with an initial diagnosis or history of CHI from all regions of Iran were recruited between 2016 and 2019. Targeted next generation sequencing (tNGS) was performed for the genes found in about half of CHI patients. Results: Mutations were identified in 24 cases (55%). Patients with a confirmed genetic cause were mainly diagnosed below age of one year old (p=0.01), had fewer other syndromic features, excluding seizure, (p=0.03), were less diazoxide responsive (p=0.04) and were more diazoxide unresponsive leading to pancreatectomy (p=0.007) compared to those with no identified mutations. Among 24 patients with identified genetic mutations, 17 (71%) had a mutation in ABCC8, 3 (12%) in KCNJ11, 3 (12%) in HADH, and 1 patient had a mutation in KMT2D. These included five novel mutations in ABCC8, KCNJ11, and KMT2D. Conclusion: This is the biggest genetic study of CHI in Iran. A high frequency of recessive forms of CHI, especially HADH mutations, in our study could be due to a high rate of consanguineous marriage. We recommend tNGS to screen for all the CHI genes. © 2022 by Turkish Pediatric Endocrinology and Diabetes Society.
Other Related Docs
16. Genotype-Phenotype Relationship in Iranian Patients With Cystic Fibrosis, Turkish Journal of Gastroenterology (2015)
17. A 3-Year-Old Boy With an Xp21 Deletion Syndrome: A Case Report, Endocrine# Metabolic and Immune Disorders - Drug Targets (2022)