A comparative phenotypic study of kallmann syndrome patients carrying monoallelic and biallelic mutations in the prokineticin 2 or prokineticin receptor 2 genes
| Autor: | Slawomir Wolczynski, Thierry Brue, Claire Bouvattier, Philippe Rondard, Isabelle Arnulf, Anne Guiochon-Mantel, F. Despert, Sylvie Cabrol, Paolo Tonella, Philippe Bouchard, Maria Ramos-Arroyo, Jean-Pierre Hardelin, Sylvie Brailly-Tabard, Michèle Mathieu, Jacques Young, Catherine Dodé, Gérard Reach, Graeme Morgan, Nathalie Chabbert-Buffet, Alfons Garcia-Piñero, James Lespinasse, Nicole De Talence, Arnaud Murat, Sébastien Jacquemont, Julie Sarfati, Bruno Delobel, Catherine Bremont, Anne Lienhardt-Roussie, Zinet Turki, Maud Bidet, Michel Pugeat, Hélène Du Boullay, Bernard Conrad |
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| Přispěvatelé: | Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), Service de génétique moléculaire, pharmacogénétique et hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Head of the Department of Medical Genetics, Département de Génétique Chromosomique, Bâtiment Hôtel Dieu - Centre Hospitalier de Chambéry, Service de génétique médicale, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Centre de Génétique Chromosomique, Hôpital Saint Vincent de Paul-GHICL, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Service d'Endocrinologie et Maladies de la reproduction, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Saint Vincent de Paul-Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL) |
| Rok vydání: | 2009 |
| Předmět: |
Male
Hydrocortisone Kallmann syndrome Endocrinology Diabetes and Metabolism Clinical Biochemistry MESH: Receptors G-Protein-Coupled medicine.disease_cause MESH: Neuropeptides Biochemistry Body Mass Index Receptors G-Protein-Coupled Basal (phylogenetics) 0302 clinical medicine Endocrinology Cryptorchidism Testis Testosterone MESH: Gastrointestinal Hormones 10. No inequality 2. Zero hunger 0303 health sciences Mutation 030219 obstetrics & reproductive medicine MESH: Testis Phenotype MESH: Hydrocortisone Circadian Rhythm Microphallus MESH: Kallmann Syndrome Female medicine.medical_specialty MESH: Mutation Receptors Peptide MESH: Testosterone Context (language use) Biology MESH: Phenotype MESH: Body Mass Index Gastrointestinal Hormones 03 medical and health sciences MESH: Cryptorchidism Internal medicine medicine Humans MESH: Circadian Rhythm Allele [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Alleles 030304 developmental biology MESH: Receptors Peptide MESH: Humans MESH: Alleles Biochemistry (medical) Neuropeptides Prokineticin receptor 2 Kallmann Syndrome medicine.disease biology.organism_classification MESH: Male MESH: Female |
| Zdroj: | Journal of Clinical Endocrinology and Metabolism Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 2010, 95 (2), pp.659-69. ⟨10.1210/jc.2009-0843⟩ Journal of Clinical Endocrinology and Metabolism, 2010, 95 (2), pp.659-69. ⟨10.1210/jc.2009-0843⟩ |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2009-0843⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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