Genetic testing facilitates prepubertal diagnosis of congenital hypogonadotropic hypogonadism.

Détails

ID Serval
serval:BIB_2FA37B7AE074
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
Genetic testing facilitates prepubertal diagnosis of congenital hypogonadotropic hypogonadism.
Périodique
Clinical genetics
Auteur(s)
Xu C., Lang-Muritano M., Phan-Hug F., Dwyer A.A., Sykiotis G.P., Cassatella D., Acierno J., Mohammadi M., Pitteloud N.
ISSN
1399-0004 (Electronic)
ISSN-L
0009-9163
Statut éditorial
Publié
Date de publication
08/2017
Peer-reviewed
Oui
Volume
92
Numéro
2
Pages
213-216
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article
Publication Status: ppublish
Résumé
Neonatal micropenis and cryptorchidism raise the suspicion of congenital hypogonadotropic hypogonadism (CHH), a rare genetic disorder caused by gonadotropin-releasing hormone deficiency. Low plasma testosterone levels and low gonadotropins during minipuberty provide a clinical diagnostic clue, yet these tests are seldomly performed in general practice. We report a male neonate with no family history of reproductive disorders who was born with micropenis and cryptorchidism. Hormonal testing at age 2.5 months showed low testosterone (0.3 nmol/L) and undetectable gonadotropins (luteinizing hormone and follicle-stimulating hormone both <0.5 U/L), suggestive of CHH. Genetic testing identified a de novo, heterozygous mutation in fibroblast growth factor receptor 1 (FGFR1 p.L630P). L630 resides on the ATP binding cleft of the FGFR1 tyrosine kinase domain, and L630P is predicted to cause a complete loss of receptor function. Cell-based assays confirmed that L630P abolishes FGF8 signaling activity. Identification of a loss-of-function de novo FGFR1 mutation in this patient confirms the diagnosis of CHH, allowing for a timely hormonal treatment to induce pubertal development. Therefore, genetic testing can complement clinical and hormonal assessment for a timely diagnosis of CHH in childhood.

Mots-clé
Congenital Abnormalities/diagnosis, Congenital Abnormalities/genetics, Congenital Abnormalities/physiopathology, Cryptorchidism/genetics, Cryptorchidism/physiopathology, Fibroblast Growth Factor 8/genetics, Genetic Testing, Gonadotropin-Releasing Hormone/deficiency, Gonadotropin-Releasing Hormone/genetics, Humans, Hypogonadism/diagnosis, Hypogonadism/genetics, Hypogonadism/physiopathology, Infant, Newborn, Male, Receptor, Fibroblast Growth Factor, Type 1/genetics, Signal Transduction, congenital hypogonadotropic hypogonadism, exome sequencing, fibroblast growth factor receptor 1, minipuberty
Pubmed
Web of science
Création de la notice
21/02/2017 18:31
Dernière modification de la notice
20/08/2019 13:14
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