Congenital Hyperinsulinism and Hypopituitarism Attributable to a Novel Mutation in FOXA2.

Congenital Hyperinsulinism and Hypopituitarism Attributable to a Novel Mutation in FOXA2.

J Clin Endocrinol Metab. 2018 Jan 10;:

Authors: Vajravelu ME, Chai J, Krock B, Baker S, Langdon D, Alter C, De León DD

Abstract
Context: Persistent hypoglycemia in the newborn period most commonly occurs due to hyperinsulinism. The phenotype of hypoketotic hypoglycemia can also result from pituitary hormone deficiencies, including growth hormone and adrenocorticotropic hormone deficiency. Forkhead box A2 (Foxa2) is a transcription factor shown in mouse models to influence insulin secretion by pancreatic beta cells. In addition, Foxa2 is involved in regulation of pituitary development, and deletions of FOXA2 have been linked to panhypopituitarism.
Objective: To describe an infant with congenital hyperinsulinism and hypopituitarism due to a mutation in FOXA2 and to determine the functional impact of the identified mutation.
Main Outcome Measure: Difference in wildtype versus mutant Foxa2 transactivation of target genes that are critical for beta cell function (ABCC8, KNCJ11, HADH) and pituitary development (GLI2, NKX2-2, SHH).
Results: Transactivation by mutant Foxa2 of all genes studied was significantly decreased compared to wild type.
Conclusions: We report a novel mutation in FOXA2 leading to congenital hyperinsulinism and hypopituitarism and provide functional evidence of the molecular mechanism for this phenotype.

PMID: 29329447 [PubMed - as supplied by publisher]

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