Investigating Genetic Mutations in a Large Cohort of Iranian Patients with Congenital Hyperinsulinism

JCRPE

Siroos Karimdadi¹  Peyman Eshraghi¹  Somayyeh Hashemian¹  Rahim Vakili¹  Parisa Tajdini²  Farzaneh Abbasi²  Saeedeh Saeedi³  Mahsa M. Amoli⁴  Maryam Razzaghy-Azar⁴  Samaneh Enayati⁴  Sepideh Borhan Dayani⁴  Hanieh Yaghootkar⁵ 

[1] Mashhad University of Medical Sciences, Faculty of Medicine, Akbar Hospital, Department of Pediatric Diseases, Mashhad, Iran;Tehran University of Medical Sciences, Children's Medical Center Hospital, Growth and Development Research Center, Tehran, Iran;Tehran University of Medical Sciences, Endocrinology and Metabolism Clinical Sciences Institute, Endocrinology and Metabolism Research Center, Tehran, Iran;Tehran University of Medical Sciences, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Metabolic Disorders Research Centre, Tehran, Iran;University of Exeter, College of Medicine and Health, Genetics of Complex Traits, London;

关键词: congenital hyperinsulinism;    genetic mutations;    diazoxide;    targeted next generation sequencing;   

DOI  :  10.4274/jcrpe.galenos.2021.2021.0071

来源: DOAJ

【 摘 要 】

INTRODUCTION: 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. DISCUSSION AND 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.

【 授权许可】

Unknown