Biallelic mutations in the prokineticin-2 gene in two sporadic cases of Kallmann syndrome.

Détails

ID Serval
serval:BIB_B161A0F04BB0
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Etude de cas (case report): rapporte une observation et la commente brièvement.
Collection
Publications
Titre
Biallelic mutations in the prokineticin-2 gene in two sporadic cases of Kallmann syndrome.
Périodique
European Journal of Human Genetics
Auteur⸱e⸱s
Leroy C., Fouveaut C., Leclercq S., Jacquemont S., Boullay H.D., Lespinasse J., Delpech M., Dupont J.M., Hardelin J.P., Dodé C.
ISSN
1018-4813 (Print)
ISSN-L
1018-4813
Statut éditorial
Publié
Date de publication
02/2008
Peer-reviewed
Oui
Volume
16
Numéro
7
Pages
865-868
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
Résumé
Kallmann syndrome is a developmental disease that combines hypogonadotropic hypogonadism and anosmia. Putative loss-of-function mutations in PROKR2 or PROK2, encoding prokineticin receptor-2 (a G protein-coupled receptor), and one of its ligands, prokineticin-2, respectively, have recently been reported in approximately 10% of Kallmann syndrome affected individuals. Notably, given PROKR2 mutations were found in the heterozygous, homozygous, or compound heterozygous state in patients, thus raising the question of a possible digenic inheritance of the disease in heterozygous patients. Indeed, one of these patients was also carrying a missense mutation in KAL1, the gene responsible for the X chromosome-linked form of Kallmann syndrome. Mutations in PROK2, however, have so far been found only in the heterozygous state. Here, we report on the identification of PROK2 biallelic mutations, that is, a missense mutation, p.R73C, and a frameshift mutation, c.163delA, in two out of 273 patients presenting as sporadic cases. We conclude that PROK2 mutations in the homozygous state account for a few cases of Kallmann syndrome. Moreover, since the same R73C mutation was previously reported in the heterozygous state, and because Prok2 knockout mice exhibit an abnormal phenotype only in the homozygous condition, we predict that patients carrying monoallelic mutations in PROK2 have another disease-causing mutation, presumably in still undiscovered Kallmann syndrome genes.
Mots-clé
Adolescent, Adult, Alleles, Animals, DNA Mutational Analysis, Female, Gastrointestinal Hormones/genetics, Humans, Kallmann Syndrome/genetics, Male, Mice, Mutation/genetics, Neuropeptides/genetics, Pedigree
Pubmed
Open Access
Oui
Création de la notice
28/02/2008 11:42
Dernière modification de la notice
20/08/2019 16:20
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