Expanding the spectrum of mutations in GH1 and GHRHR: genetic screening in a large cohort of patients with congenital isolated growth hormone deficiency.
Alatzoglou, Kyriaki S Turton, James P Kelberman, Daniel Clayton, Peter E Mehta, Ameeta Buchanan, Charles Aylwin, Simon Crowne, Elizabeth C Christesen, Henrik T Hertel, Niels T
Alatzoglou, Kyriaki S
Turton, James P
Kelberman, Daniel
Clayton, Peter E
Mehta, Ameeta
Buchanan, Charles
Aylwin, Simon
Crowne, Elizabeth C
Christesen, Henrik T
Hertel, Niels T
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Abstract
CONTEXT: It is estimated that 3-30% of cases with isolated GH deficiency (IGHD) have a genetic etiology, with a number of mutations being reported in GH1 and GHRHR. The aim of our study was to genetically characterize a cohort of patients with congenital IGHD and analyze their characteristics. PATIENTS AND METHODS: A total of 224 patients (190 pedigrees) with IGHD and a eutopic posterior pituitary were screened for mutations in GH1 and GHRHR. To explore the possibility of an association of GH1 abnormalities with multiple pituitary hormone deficiencies, we have screened 62 patients with either multiple pituitary hormone deficiencies (42 pedigrees), or IGHD with an ectopic posterior pituitary (21 pedigrees). RESULTS: Mutations in GH1 and GHRHR were identified in 41 patients from 21 pedigrees (11.1%), with a higher prevalence in familial cases (38.6%). These included previously described and novel mutations in GH1 (C182X, G120V, R178H, IVS3+4nt, a>t) and GHRHR (W273S, R94L, R162W). Autosomal dominant, type II IGHD was the commonest form (52.4%), followed by type IB (42.8%) and type IA (4.8%). Patients with type II IGHD had highly variable phenotypes. There was no difference in the endocrinology or magnetic resonance imaging appearance between patients with and without mutations, although those with mutations presented with more significant growth failure (height, -4.7 +/- 1.6 SDS vs. -3.4 +/- 1.7 SDS) (P = 0.001). There was no apparent difference between patients with mutations in GH1 and GHRHR. CONCLUSIONS: IGHD patients with severe growth failure and a positive family history should be screened for genetic mutations; the evolving endocrinopathy observed in some of these patients suggests the need for long-term follow-up.
Authors
Alatzoglou, Kyriaki S
Turton, James P
Kelberman, Daniel
Clayton, Peter E
Mehta, Ameeta
Buchanan, Charles
Aylwin, Simon
Crowne, Elizabeth C
Christesen, Henrik T
Hertel, Niels T
Trainer, Peter J
Savage, Martin O
Raza, Jamal
Banerjee, Kausik
Sinha, Sunil K
Ten, Svetlana
Mushtaq, Talat
Brauner, Raja
Cheetham, Timothy D
Hindmarsh, Peter C
Mullis, Primus E
Dattani, Mehul T
Turton, James P
Kelberman, Daniel
Clayton, Peter E
Mehta, Ameeta
Buchanan, Charles
Aylwin, Simon
Crowne, Elizabeth C
Christesen, Henrik T
Hertel, Niels T
Trainer, Peter J
Savage, Martin O
Raza, Jamal
Banerjee, Kausik
Sinha, Sunil K
Ten, Svetlana
Mushtaq, Talat
Brauner, Raja
Cheetham, Timothy D
Hindmarsh, Peter C
Mullis, Primus E
Dattani, Mehul T
Description
Date
2009-09
Publisher
Collections
Keywords
Type
Article
Citation
Expanding the spectrum of mutations in GH1 and GHRHR: genetic screening in a large cohort of patients with congenital isolated growth hormone deficiency. 2009, 94 (9):3191-9 J. Clin. Endocrinol. Metab.