The Journal of clinical endocrinology and metabolism · 2018
Congenital Hyperinsulinism and Hypopituitarism Attributable to a Mutation in FOXA2.
Клинический случайСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Vajravelu Mary Ellen, Chai Jinghua, Krock Bryan, Baker Samuel, Langdon David, Alter Craig, De León Diva D
Аннотация
CONTEXT: Persistent hypoglycemia in the newborn period most commonly occurs as a result of 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 β 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 as a result of a mutation in FOXA2 and to determine the functional impact of the identified mutation.
MAIN OUTCOME MEASURE: Difference in wild-type (WT) vs mutant Foxa2 transactivation of target genes that are critical for β cell function (ABCC8, KNCJ11, HADH) and pituitary development (GLI2, NKX2-2, SHH).
RESULTS: Transactivation by mutant Foxa2 of all genes studied was substantially decreased compared with WT.
CONCLUSIONS: We report a mutation in FOXA2 leading to congenital hyperinsulinism and hypopituitarism and provide functional evidence of the molecular mechanism responsible for this phenotype.
OBJECTIVE: To describe an infant with congenital hyperinsulinism and hypopituitarism as a result of a mutation in FOXA2 and to determine the functional impact of the identified mutation.
MAIN OUTCOME MEASURE: Difference in wild-type (WT) vs mutant Foxa2 transactivation of target genes that are critical for β cell function (ABCC8, KNCJ11, HADH) and pituitary development (GLI2, NKX2-2, SHH).
RESULTS: Transactivation by mutant Foxa2 of all genes studied was substantially decreased compared with WT.
CONCLUSIONS: We report a mutation in FOXA2 leading to congenital hyperinsulinism and hypopituitarism and provide functional evidence of the molecular mechanism responsible for this phenotype.