FGFR1 and PROKR2 rare variants found in patients with combined pituitary hormone deficiencies.

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Ressource 1Télécharger: BIB_4C5F67BEEDF1.P001.pdf (349.40 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_4C5F67BEEDF1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
FGFR1 and PROKR2 rare variants found in patients with combined pituitary hormone deficiencies.
Périodique
Endocrine Connections
Auteur(s)
Correa F.A., Trarbach E.B., Tusset C., Latronico A.C., Montenegro L.R., Carvalho L.R., Franca M.M., Otto A.P., Costalonga E.F., Brito V.N., Abreu A.P., Nishi M.Y., Jorge A.A., Arnhold I.J., Sidis Y., Pitteloud N., Mendonca B.B.
ISSN
2049-3614 (Electronic)
ISSN-L
2049-3614
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
4
Numéro
2
Pages
100-107
Langue
anglais
Résumé
The genetic aetiology of congenital hypopituitarism (CH) is not entirely elucidated. FGFR1 and PROKR2 loss-of-function mutations are classically involved in hypogonadotrophic hypogonadism (HH), however, due to the clinical and genetic overlap of HH and CH; these genes may also be involved in the pathogenesis of CH. Using a candidate gene approach, we screened 156 Brazilian patients with combined pituitary hormone deficiencies (CPHD) for loss-of-function mutations in FGFR1 and PROKR2. We identified three FGFR1 variants (p.Arg448Trp, p.Ser107Leu and p.Pro772Ser) in four unrelated patients (two males) and two PROKR2 variants (p.Arg85Cys and p.Arg248Glu) in two unrelated female patients. Five of the six patients harbouring the variants had a first-degree relative that was an unaffected carrier of it. Results of functional studies indicated that the new FGFR1 variant p.Arg448Trp is a loss-of-function variant, while p.Ser107Leu and p.Pro772Ser present signalling activity similar to the wild-type form. Regarding PROKR2 variants, results from previous functional studies indicated that p.Arg85Cys moderately compromises receptor signalling through both MAPK and Ca(2) (+) pathways while p.Arg248Glu decreases calcium mobilization but has normal MAPK activity. The presence of loss-of-function variants of FGFR1 and PROKR2 in our patients with CPHD is indicative of an adjuvant and/or modifier effect of these rare variants on the phenotype. The presence of the same variants in unaffected relatives implies that they cannot solely cause the phenotype. Other associated genetic and/or environmental modifiers may play a role in the aetiology of this condition.
Pubmed
Open Access
Oui
Création de la notice
13/01/2016 14:42
Dernière modification de la notice
20/08/2019 15:00
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