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

• Published in: Journal of clinical research in pediatric endocrinology 2022-03, Vol.14 (1), p.87-95
• Main Authors: Razzaghy-Azar, Maryam, Saeedi, Saeedeh, Dayani, Sepideh Borhan, Enayati, Samaneh, Abbasi, Farzaneh, Hashemian, Somayyeh, Eshraghi, Peyman, Karimdadi, Siroos, Tajdini, Parisa, Vakili, Rahim, Amoli, Mahsa M., Yaghootkar, Hanieh
• Format: Article
• Language: English
• Subjects: Child; Congenital hyperinsulinism; Congenital Hyperinsulinism - diagnosis; Congenital Hyperinsulinism - genetics; Development and progression; Diazoxide; Female; Gene mutations; Genetic aspects; genetic mutations; Health aspects; Humans; Infant; Insulin; Iran; Male; Medical Engineering; Medicinsk teknik; Metabolic diseases; Mutation; Original; Pediatric research; Physiological aspects; Sulfonylurea Receptors - genetics; targeted next generation sequencing
• ISSN: 1308-5727; 1308-5735; 1308-5735
• DOI: 10.4274/jcrpe.galenos.2021.2021.0071

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. 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. 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 , 3 (12%) in , 3 (12%) in , and 1 patient had a mutation in . These included five novel mutations in , and . 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.