Absence of GH-Releasing Hormone (GHRH) Mutations in Selected Patients with Isolated GH Deficiency
Carregando...
Citações na Scopus
18
Tipo de produção
article
Data de publicação
2011
Título da Revista
ISSN da Revista
Título do Volume
Editora
ENDOCRINE SOC
Autores
ALATZOGLOU, Kyriaki S.
AUDI, Laura
CARRASCOSA, Antonio
DATTANI, Mehul T.
Citação
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v.96, n.9, p.E1457-E1460, 2011
Resumo
Context: Although numerous reports of mutations in GH1 and GHRHR (GHRH receptor) causing isolated GH deficiency (IGHD) have been published, mutations in GHRH itself have not been hitherto reported but are obvious candidates for GH deficiency. Objective: The aim of this study was to identify mutations in GHRH in a large cohort of patients with IGHD. Patients and Methods: DNA was isolated from 151 patients diagnosed with IGHD at national and international centers. Seventy-two patients fulfilled all the following criteria: severe short stature (height SD score <= -2.5), low peakGHafter stimulation (peak <= 5 ng/ml), eutopic posterior pituitary lobe, and absence of mutations in GH1 and GHRHR and therefore were strong candidates for GHRH mutations. The coding sequence and splice sites of GHRH were amplified by PCR with intronic primers and sequenced. Results: In five of 151 patients (four of 42 from Brazil), the GHRH c. 223 C>T, p. L75F change was identified in heterozygosity. This variant has been previously reported as a polymorphism and is more frequent in African than European and Asian populations. Six allelic variants (five novel) that do not predict change of amino acids or splice sites were identified in five patients: c. 147 C>T, p.S49S, IVS1 -70 G>A, IVS1 -74 T>C, IVS3 -47 del1, and IVS3 +7 G>A/IVS3 + 41 G>A. No functional mutations were found in this cohort. Conclusions: GHRH mutations were not identified in a selected cohort of patients with IGHD, suggesting that, if they exist, they may be an extremely rare cause of IGHD. Other, as-yet-unidentified genetic factors may be implicated in the genetic etiology of IGHD in our cohort. (J Clin Endocrinol Metab 96: E1457-E1460, 2011)
Palavras-chave
Referências
- LINDSAY R, 1994, J PEDIATR-US, V125, P29, DOI 10.1016/S0022-3476(94)70117-2
- Chan YM, 2009, P NATL ACAD SCI USA, V106, P11703, DOI 10.1073/pnas.0903449106
- Arnhold IJ, 2009, HORM RES, V71, P75, DOI 10.1159/000183895
- Pantel J, 2009, J CLIN ENDOCR METAB, V94, P4334, DOI 10.1210/jc.2009-1327
- Parra FC, 2003, P NATL ACAD SCI USA, V100, P177, DOI 10.1073/pnas.0126614100
- Alatzoglou KS, 2010, NAT REV ENDOCRINOL, V6, P562, DOI 10.1038/nrendo.2010.147
- Bouligand J, 2009, NEW ENGL J MED, V360, P2742, DOI 10.1056/NEJMoa0900136
- Pantel J, 2006, J CLIN INVEST, V116, P760, DOI 10.1172/JCI25303
- Alatzoglou KS, 2009, J CLIN ENDOCR METAB, V94, P3191, DOI 10.1210/jc.2008-2783
- Osorio MGF, 2002, J CLIN ENDOCR METAB, V87, P5076, DOI 10.1210/jc.2001-011936
- Alba M, 2004, ENDOCRINOLOGY, V145, P4134, DOI 10.1210/en.2004-0119
- [Anonymous], 2003, NATURE, V426, P789
- Esteban C, 2007, CLIN ENDOCRINOL, V66, P258, DOI 10.1111/j.1365-2265.2006.02718.x
- Melmed S., 2008, WILLIAMS TXB ENDOCRI, P155
- Mohamadi A, 2009, J CLIN ENDOCR METAB, V94, P2565, DOI 10.1210/jc.2009-0512
- MULLIS P, 1990, J CLIN ENDOCR METAB, V70, P187
- JURADO LAP, 1994, J CLIN ENDOCR METAB, V78, P622
- REITER EO, 2008, WILLIAMS TXB ENDOCRI, P849
- Silva EGP, 2003, HORM RES, V59, P229, DOI 10.1159/000070222
- THORNER MO, 1988, PEDIATR RES, V24, P145, DOI 10.1203/00006450-198808000-00001