| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
Submitted on March 14, 2005
Accepted on May 20, 2005
Biochemistry, Endocrinology and Metabolism Unit and London Centre for Paediatric Endocrinology, Institute of Child Health, London, UK (JPGT, AM, KSW, MTD); Unite Mixte de Recherche 6544, Centre National de la Recherche Scientifique, Universite de la Mediterranee, Institut Federatif de Recherche Jean-Roche, Faculte de Medecine Nord, Marseille, France (RR, AS, TB); St.Luke's Hospital, Department of Paediatrics, Guardamangia, Malta (JT, SAM, RP, CV); National Endocrinological Research Centre, Paediatric Unit, Moscow, Russian Federation (AT); Division of Endocrinology, Hospital for Sick Children, Toronto, Canada (VZ, JH); Royal Manchester Children's Hospital, Pendlebury, Manchester, UK (PEC); Department of Endocrinology, Christie Hospital, Wilmslow Road, Manchester, UK (SS); Royal Gwent Hospital, Newport, UK (JB)
* To whom correspondence should be addressed. E-mail: mdattani{at}ich.ucl.ac.uk.
CONTEXT: 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 growth hormone deficiency (IGHD) for mutations within POU1F1.
RESULTS: Causative mutations were identified in 10/129 individuals (7.8%). Of these, 5 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 bp (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 3 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 which had been commenced unnecessarily. These data reflect the importance of mutational analysis in patients with CPHD
This article has been cited by other articles:
 |
|
 |
|
  D. Kelberman and M. T. Dattani Hypothalamic and pituitary development: novel insights into the aetiology Eur. J. Endocrinol., August 1, 2007; 157(suppl_1): S3 - S14. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. G. McNay, J. P. Turton, D. Kelberman, K. S. Woods, R. Brauner, A. Papadimitriou, E. Keller, A. Keller, N. Haufs, H. Krude, et al. HESX1 Mutations Are an Uncommon Cause of Septooptic Dysplasia and Hypopituitarism J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 691 - 697. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Miyata, S. Vallette-Kasic, A. Saveanu, M. Takeuchi, H. Yoshikawa, A. Tajima, K. Tojo, R. Reynaud, M. Gueydan, A. Enjalbert, et al. Identification and Functional Analysis of the Novel S179R POU1F1 Mutation Associated with Combined Pituitary Hormone Deficiency J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 4981 - 4987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Reynaud, M. Gueydan, A. Saveanu, S. Vallette-Kasic, A. Enjalbert, T. Brue, and A. Barlier Genetic Screening of Combined Pituitary Hormone Deficiency: Experience in 195 Patients J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3329 - 3336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. P. S. Bhangoo, C. S. Hunter, J. J. Savage, H. Anhalt, S. Pavlakis, E. C. Walvoord, S. Ten, and S. J. Rhodes A Novel LHX3 Mutation Presenting as Combined Pituitary Hormonal Deficiency J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 747 - 753. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
