A comparative phenotypic study of kallmann syndrome patients carrying monoallelic and biallelic mutations in the prokineticin 2 or prokineticin receptor 2 genes.

Détails

ID Serval
serval:BIB_D6B7F69B2004
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A comparative phenotypic study of kallmann syndrome patients carrying monoallelic and biallelic mutations in the prokineticin 2 or prokineticin receptor 2 genes.
Périodique
Journal of Clinical Endocrinology and Metabolism
Auteur⸱e⸱s
Sarfati Julie, Guiochon-Mantel Anne, Rondard Philippe, Arnulf Isabelle, Garcia-Pinero Alfons, Brailly-Tabard Sylvie, Bidet Maud, Ramos-Arroyo Maria, Mathieu Michele, Lienhardt-Roussie Anne, Morgan Graeme, Turki Zinet, Bremont Catherine, Lespinasse James, Du Boullay Helene, Chabbert-Buffet Nathalie, Jacquemont Sebastien, Reach Gerard, De Talence Nicole, Tonella Paolo, Conrad Bernard, Despert Francois, Delobel Bruno, Brue Thierry, Bouvattier Claire, Cabrol Sylvie, Pugeat Michel, Murat Arnaud, Bouchard Philippe, Hardelin Jean-Pierre, Dode Catherine, Young Jacques
Collaborateur⸱rice⸱s
Wolczynski Slawomir)
ISSN
1945-7197[electronic], 0021-972X[linking]
Statut éditorial
Publié
Date de publication
2010
Volume
95
Numéro
2
Pages
659-669
Langue
anglais
Résumé
Context: Both biallelic and monoallelic mutations in PROK2 or PROKR2 have been found in Kallmann syndrome (KS). Objective: The objective of the study was to compare the phenotypes of KS patients harboring monoallelic and biallelic mutations in these genes. Design and Patients: We studied clinical and endocrine features that reflect the functioning of the pituitary-gonadal axis, and the nonreproductive phenotype, in 55 adult KS patients (42 men and 13 women), of whom 41 had monoallelic mutations and 14 biallelic mutations in PROK2 or PROKR2. Results: Biallelic mutations were associated with more frequent cryptorchidism (70% vs. 34%, P < 0.05) and microphallus (90% vs. 28%, P < 0.001) and lower mean testicular volume (1.2 +/- 0.4 vs. 4.5 +/- 6.0 ml; P < 0.01) in male patients. Likewise, the testosterone level as well as the basal FSH level and peak LH level under GnRH-stimulation were lower in males with biallelic mutations (0.2 +/- 0.1 vs. 0.7 +/- 0.8 ng/ml; P = 0.05, 0.3 +/- 0.1 vs. 1.8 +/- 3.0 IU/liter; P < 0.05, and 0.8 +/- 0.8 vs. 5.2 +/- 5.5 IU/liter; P < 0.05, respectively). Nonreproductive, nonolfactory anomalies were rare in both sexes and were never found in patients with biallelic mutations. The mean body mass index of the patients (23.9 +/- 4.2 kg/m(2) in males and 26.3 +/- 6.6 kg/m(2) in females) did not differ significantly from that of gender-, age-, and treatment-matched KS individuals who did not carry a mutation in PROK2 or PROKR2. Finally, circadian cortisol levels evaluated in five patients, including one with biallelic PROKR2 mutations, were normal in all cases. Conclusion: Male patients carrying biallelic mutations in PROK2 or PROKR2 have a less variable and on average a more severe reproductive phenotype than patients carrying monoallelic mutations in these genes. Nonreproductive, nonolfactory clinical anomalies associated with KS seem to be restricted to patients with monoallelic mutations.
Mots-clé
Idiopathic Hypogonadotropic Hypogonadism, Gonadotropin-Releasing-Hormone, Of-Function Mutations, Encoding Prokineticin-2, Candidate Gene, Mice Lacking, Deficiency, Molecules, Adhesion, Protein
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/02/2010 11:31
Dernière modification de la notice
20/08/2019 16:56
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