| Title | Expanding the Spectrum of Mutations in GH1 and GHRHR: Genetic Screening in a Large Cohort of Patients with Congenital Isolated Growth Hormone Deficiency. | | 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 | | Institution | Developmental Endocrinology Research Group, Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London UK; Endocrine Sciences Research Group, University of Manchester, UK; Departments of Child Health and Endocrinology, King's College Hospital, London UK; Department of Pediatric Diabetes and Endocrinology, Bristol Royal Hospital for Children, University Hospitals Bristol NHS Foundation Trust, Bristol, UK; Department of Pediatrics, H.C Andersen Children's Hospital, Odense University Hospital, Denmark; Department of Endocrinology, Christie Hospital, Manchester, UK; Department of Pediatric Endocrinology, William Harvey Research Institute, Barts and The London Queen Mary's School of Medicine and Dentistry, London UK; Department of Endocrinology, National Institute of Child Health, Karachi, Pakistan; Department of Paediatrics, Whipps Cross University Hospital, London UK; Division of Pediatric Endocrinology, Maimonides Infants' and Children Hospital of Brooklyn and SUNY Downstate, NY, USA; Department of Pediatric Endocrinology, Leeds University Teaching Hospitals, Leeds General Infirmary, UK; Department of Pediatric Endocrinology, Hôpital Bicêtre, Université Paris Descartes, France; Institute of Human Genetics, Newcastle University, Royal Victoria Infirmary, Newcastle upon Tyne, UK; Pediatric Endocrinology, University Children's Hospital Inselspital, Bern, Switzerland. | | Source | J Clin Endocrinol Metab 2009 Jun 30. | | Abstract | Context: It is estimated that 3-30% of cases with 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: 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 MRI 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19567534 |
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