Toggle Main Menu Toggle Search

Open Access padlockePrints

Expanding the Spectrum of Mutations in GH1 and GHRHR: Genetic Screening in a Large Cohort of Patients with Congenital Isolated Growth Hormone Deficiency

Lookup NU author(s): Professor Sunil Sinha, Professor Timothy Cheetham

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


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. (J Clin Endocrinol Metab 94: 3191-3199, 2009)


Publication metadata

Author(s): Alatzoglou KS, Turton JP, Kelberman D, Clayton PE, Mehta A, Buchanan C, Aylwin S, Crowne EC, Christesen HT, Hertel NT, Trainer PJ, Savage MO, Raza J, Banerjee K, Sinha SK, Ten S, Mushtaq T, Brauner R, Cheetham TD, Hindmarsh PC, Mullis PE, Dattani MT

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Endocrinology and Metabolism

Year: 2009

Volume: 94

Issue: 9

Pages: 3191-3199

ISSN (print): 0021-972X

ISSN (electronic): 1945-7197

Publisher: The Endocrine Society

URL: http://dx.doi.org/10.1210/jc.2008-2783

DOI: 10.1210/jc.2008-2783


Altmetrics

Altmetrics provided by Altmetric


Share