| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
CLINICAL STUDY |
1 Institute of Reproductive Medicine of the University, D-48129 Münster, Germany and 2 Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Torino, Italy
(Correspondence should be addressed to E Nieschlag; Email: Eberhard.Nieschlag{at}ukmuenster.de)
Objective: To determine the frequency of mutations of the gonadotropin-releasing hormone receptor (GnRHR) and of the G protein-coupled receptor 54 (GPR54) genes in normosmic idiopathic hypogonadotropic hypogonadism (IHH).
Methods: In a retrospective study we analyzed the GnRHR and the GPR54 genes of 45 IHH patients and 50 controls. Genomic DNA was amplified by PCR to obtain partially overlapping amplicons encompassing the exon–intron boundaries of the GnRHR and GPR54 genes and analyzed by single-stranded conformation polymorphism gel electrophoresis and/or DNA sequencing.
Results: One heterozygous R262Q mutation of the GnRHR gene was identified in one patient with familial IHH. The silent single-nucleotide polymorphism (SNP) 453C > T occurred at the same frequency in patients and controls. One patient with sporadic IHH and consanguineous parents showed a novel homozygous sequence variation of the GPR54 gene (1001_1002insC) resulting in an open reading frame shift and elongation of 43 amino acids with an increased number of proline residues in the intracellular receptor domain. This patient had delayed puberty, low testosterone (3.4 nmol/l), and low-normal LH and FSH levels responsive to GnRH. Pulsatile GnRH administration normalized testosterone levels and induced spermatogenesis sufficiently to induce a pregnancy with assisted reproduction. Two common SNPs in exon 1 and exon 5 of the GPR54 gene showed similar frequency distribution and hormonal profiles in IHH and controls.
Conclusions: Mutations of the GnRHR and of the GPR54 gene are rare in IHH and should be investigated especially in cases with autosomal recessive transmission. Common SNPs of the GnRHR and GPR54 genes do not play any role in IHH.
This article has been cited by other articles:
|
|
 |
|
  E. Gianetti and S. Seminara Kisspeptin and KISS1R: a critical pathway in the reproductive system Reproduction, September 1, 2008; 136(3): 295 - 301. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. d'Anglemont de Tassigny, L. A. Fagg, J. P. C. Dixon, K. Day, H. G. Leitch, A. G. Hendrick, D. Zahn, I. Franceschini, A. Caraty, M. B. L. Carlton, et al. Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene PNAS, June 19, 2007; 104(25): 10714 - 10719. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Tenenbaum-Rakover, M. Commenges-Ducos, A. Iovane, C. Aumas, O. Admoni, and N. de Roux Neuroendocrine Phenotype Analysis in Five Patients with Isolated Hypogonadotropic Hypogonadism due to a L102P Inactivating Mutation of GPR54 J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 1137 - 1144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Cerrato, J. Shagoury, M. Kralickova, A. Dwyer, J. Falardeau, M. Ozata, G. Van Vliet, P. Bouloux, J. E Hall, F. J Hayes, et al. Coding sequence analysis of GNRHR and GPR54 in patients with congenital and adult-onset forms of hypogonadotropic hypogonadism Eur. J. Endocrinol., November 1, 2006; 155(suppl_1): S3 - S10. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Tena-Sempere GPR54 and kisspeptin in reproduction Hum. Reprod. Update, September 1, 2006; 12(5): 631 - 639. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
