Genotype and Phenotype Correlations in 417 Children With Congenital Hyperinsulinism

Abstract

Genotype to phenotype correlations were most successful in children with GLUD1, GCK, and recessive KATP mutations. Correlations were complicated by the high frequency of novel missense KATP mutations that were uncharacterized, because such defects might be either recessive or dominant and, if dominant, be either responsive or unresponsive to diazoxide. Accurate and timely prediction of phenotype based on genotype is critical to limit exposure to persistent hypoglycemia in infants and children with congenital HI.

Clinical and histological heterogeneity of congenital hyperinsulinism due to paternally inherited heterozygous ABCC8/KCNJ11 mutations

“…Mutations in the ABCC8/KCNJ11, which account for the majority of genetically confirmed CHI cases, can either be biallelic or monoallelic (3,4,37). Biallelic ABCC8/KCNJ11 mutations result in diffuse CHI, whereas monoallelic mutations can either be asymptomatic (38).…”

“…Mutations in nine different genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, subunits: Kir6.2 encoded by KCNJ11 and SUR1 encoded by ABCC8 gene (2). Both genes are localised in the 11p15.1 region and mutations in these accounts for the majority of CHI patients (3,4,5,6,7,8,9,10,11).…”

Wrodzony hiperinsulinizm — próba optymalizacji diagnostyki i leczenia u polskich pacjentów

“…It comprises a heterogenic group of insulin secretion defects, and it is characterised by diverse molecular aetiology, histological features, severity of symptoms, and response to pharmacological treatment [1][2][3].…”

“…Molecular analysis introduced in the last decade has revolutionised diagnosis and clinical care of CHI [3,5,6]. In many centres identification of the genetic background of CHI has become strategic in planning further therapy: conservative treatment or radical surgical resection.…”

“…Mutations in eight genes (ABCC8, KCNJ11, GLUD1, GCK, HNF4A, HADH, SLC16A1, and UCP2) have been described as related to CHI. Mutations in these genes are usually recognised in 50-80% of patients, depending on the screened population and the applied genetic methods [3,[7][8][9]. In the remaining 20-50% of patients the genetic cause of hypoglycaemia is still unknown [1,7].…”