A Novel Mutation in Insulin-Like Growth Factor 1 Receptor (c.641-2A & #x3e;G) Is Associated with Impaired Growth, Hypoglycemia, and Modified Immune Phenotypes

We report on a family presenting with a novel heterozygousIGF1R mutation with characterization of the mutation, IGF1R expression, and immune phenotyping. Twin probands presented clinically with short stature and hypoglycemia. Variable phenotypic expression was seen in 2 other family members carrying theIGF1R mutation. The probands were treated with exogenous growth hormone therapy and dietary cornstarch, improving linear growth and reducing hypoglycemic events.IGF1R c.641-2A#x3e;G caused abnormal mRNA splicing and premature protein termination. Flow cytometric immunophenotyping demonstrated lower IGF1R on peripheral blood mononuclear cells fromIGF1R c.641-2A#x3e;G subjects. This alteration was associated with reduced levels of T-helper 17 cells and a higher percentage of T-helper 1 cells compared to controls, suggesting decreased IGF1R expression may affect CD4+ Th-cell lineage commitment.Discussion: Collectively, these data suggest a novel loss-of-function mutation (c.641-2A#x3e;G) leads to aberrant mRNA splicing and IGF1R expression resulting in hypoglycemia, growth restriction, and altered immune phenotypes.Horm Res Paediatr

Source: Hormone Research in Paediatrics - October 28, 2020 Category: Endocrinology Source Type: research