Novel mutations within the POU1F1 gene associated with variable combined pituitary hormone deficiency.
AuthorsTurton, James P
Woods, Kathryn S
Clayton, Peter E
Shalet, Stephen M
Dattani, Mehul T
AffiliationBiochemistry, Endocrinology, and Metabolism Unit and London Centre for Paediatric Endocrinology, Institute of Child Health, London, United Kingdom.
MetadataShow full item record
AbstractCONTEXT: Mutations within the gene encoding the pituitary-specific transcription factor POU1F1 are associated with combined pituitary hormone deficiency (CPHD). Most of the affected individuals manifest GH, prolactin, and TSH deficiency. OBJECTIVE: We have now screened 129 individuals with CPHD and isolated GH deficiency for mutations within POU1F1. RESULTS: Causative mutations were identified in 10 of 129 individuals (7.8%). Of these, five patients harbored the dominant negative R271W mutation, which is a well-recognized mutational hot spot. We have also identified a second frequently occurring mutation, E230K, which appears to be common in Maltese patients. Additionally, we describe two novel mutations within POU1F1, an insertion of a single base pair (ins778A) and a missense mutation (R172Q). Functional studies have revealed that POU1F1 (E230K) is associated with a reduction in transactivation, although DNA-binding affinity is similar to the wild-type protein. On the other hand, POU1F1 (R172Q) is associated with a reduction in DNA binding and transactivation, whereas POU1F1 (ins778A) is associated with loss of DNA binding and a reduction in transactivation. CONCLUSIONS: Our data suggest that the phenotype associated with POU1F1 mutations may be more variable, with the occasional preservation of TSH secretion. Additionally, our data revealed POU1F1 mutations in three patients who were diagnosed as having ACTH deficiency but who, on further evaluation, were found to have normal cortisol secretion. Hence, elucidation of the genotype led to further evaluation of the phenotype, with the cessation of cortisol replacement that had been commenced unnecessarily. These data reflect the importance of mutational analysis in patients with CPHD.
CitationNovel mutations within the POU1F1 gene associated with variable combined pituitary hormone deficiency. 2005, 90 (8):4762-70 J. Clin. Endocrinol. Metab.
JournalThe Journal of Clinical Endocrinology and Metabolism
- Two novel mutations in the POU1F1 gene generate null alleles through different mechanisms leading to combined pituitary hormone deficiency.
- Authors: Turton JP, Strom M, Langham S, Dattani MT, Le Tissier P
- Issue date: 2012 Mar
- GH transcription factors.
- Authors: Pfaffle RW, Kim C, Blankenstein O, Kentrup H
- Issue date: 1999 Apr
- The de novo Q167K mutation in the POU1F1 gene leads to combined pituitary hormone deficiency in an Italian patient.
- Authors: Malvagia S, Poggi GM, Pasquini E, Donati MA, Pela I, Morrone A, Zammarchi E
- Issue date: 2003 Nov
- Functional characterization of a human POU1F1 mutation associated with isolated growth hormone deficiency: a novel etiology for IGHD.
- Authors: Sobrier ML, Tsai YC, Pérez C, Leheup B, Bouceba T, Duquesnoy P, Copin B, Sizova D, Penzo A, Stanger BZ, Cooke NE, Liebhaber SA, Amselem S
- Issue date: 2016 Feb 1
- Identification and functional analysis of the novel S179R POU1F1 mutation associated with combined pituitary hormone deficiency.
- Authors: Miyata I, Vallette-Kasic S, Saveanu A, Takeuchi M, Yoshikawa H, Tajima A, Tojo K, Reynaud R, Gueydan M, Enjalbert A, Tajima N, Eto Y, Brue T
- Issue date: 2006 Dec