Expanding the spectrum of mutations in GH1 and GHRHR: genetic screening in a large cohort of patients with congenital isolated growth hormone deficiency.

2.50
Hdl Handle:
http://hdl.handle.net/10541/84997
Title:
Expanding the spectrum of mutations in GH1 and GHRHR: genetic screening in a large cohort of patients with congenital isolated growth hormone deficiency.
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
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.
Affiliation:
Developmental Endocrinology Research Group, Clinical and Molecular Genetics Unit, University College London Institute of Child Health, London WC1N 1EH, United Kingdom.
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.
Journal:
The Journal of Clinical Endocrinology and Metabolism
Issue Date:
Sep-2009
URI:
http://hdl.handle.net/10541/84997
DOI:
10.1210/jc.2008-2783
PubMed ID:
19567534
Type:
Article
Language:
en
ISSN:
1945-7197
Appears in Collections:
All Christie Publications ; Endocrinology

Full metadata record

DC FieldValue Language
dc.contributor.authorAlatzoglou, Kyriaki Sen
dc.contributor.authorTurton, James Pen
dc.contributor.authorKelberman, Danielen
dc.contributor.authorClayton, Peter Een
dc.contributor.authorMehta, Ameetaen
dc.contributor.authorBuchanan, Charlesen
dc.contributor.authorAylwin, Simonen
dc.contributor.authorCrowne, Elizabeth Cen
dc.contributor.authorChristesen, Henrik Ten
dc.contributor.authorHertel, Niels Ten
dc.contributor.authorTrainer, Peter Jen
dc.contributor.authorSavage, Martin Oen
dc.contributor.authorRaza, Jamalen
dc.contributor.authorBanerjee, Kausiken
dc.contributor.authorSinha, Sunil Ken
dc.contributor.authorTen, Svetlanaen
dc.contributor.authorMushtaq, Talaten
dc.contributor.authorBrauner, Rajaen
dc.contributor.authorCheetham, Timothy Den
dc.contributor.authorHindmarsh, Peter Cen
dc.contributor.authorMullis, Primus Een
dc.contributor.authorDattani, Mehul Ten
dc.date.accessioned2009-10-29T10:40:24Z-
dc.date.available2009-10-29T10:40:24Z-
dc.date.issued2009-09-
dc.identifier.citationExpanding 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.en
dc.identifier.issn1945-7197-
dc.identifier.pmid19567534-
dc.identifier.doi10.1210/jc.2008-2783-
dc.identifier.urihttp://hdl.handle.net/10541/84997-
dc.description.abstractCONTEXT: 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.en
dc.language.isoenen
dc.subject.meshAdolescent-
dc.subject.meshChild-
dc.subject.meshChild, Preschool-
dc.subject.meshCohort Studies-
dc.subject.meshGenetic Screening-
dc.subject.meshHomeodomain Proteins-
dc.subject.meshHuman Growth Hormone-
dc.subject.meshHumans-
dc.subject.meshInfant-
dc.subject.meshLocus Control Region-
dc.subject.meshMutation-
dc.subject.meshPedigree-
dc.subject.meshReceptors, Neuropeptide-
dc.subject.meshReceptors, Pituitary Hormone-Regulating Hormone-
dc.subject.meshSOXB1 Transcription Factors-
dc.titleExpanding the spectrum of mutations in GH1 and GHRHR: genetic screening in a large cohort of patients with congenital isolated growth hormone deficiency.en
dc.typeArticleen
dc.contributor.departmentDevelopmental Endocrinology Research Group, Clinical and Molecular Genetics Unit, University College London Institute of Child Health, London WC1N 1EH, United Kingdom.en
dc.identifier.journalThe Journal of Clinical Endocrinology and Metabolismen

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