Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures.

Détails

ID Serval
serval:BIB_92D278111021
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures.
Périodique
European journal of endocrinology
Auteur(s)
Cassatella D., Howard S.R., Acierno J.S., Xu C., Papadakis G.E., Santoni F.A., Dwyer A.A., Santini S., Sykiotis G.P., Chambion C., Meylan J., Marino L., Favre L., Li J., Liu X., Zhang J., Bouloux P.M., Geyter C., Paepe A., Dhillo W.S., Ferrara J.M., Hauschild M., Lang-Muritano M., Lemke J.R., Flück C., Nemeth A., Phan-Hug F., Pignatelli D., Popovic V., Pekic S., Quinton R., Szinnai G., l'Allemand D., Konrad D., Sharif S., Iyidir Ö.T., Stevenson B.J., Yang H., Dunkel L., Pitteloud N.
ISSN
1479-683X (Electronic)
ISSN-L
0804-4643
Statut éditorial
Publié
Date de publication
04/2018
Peer-reviewed
Oui
Volume
178
Numéro
4
Pages
377-388
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) represent rare and common forms of GnRH deficiency, respectively. Both CDGP and CHH present with delayed puberty, and the distinction between these two entities during early adolescence is challenging. More than 30 genes have been implicated in CHH, while the genetic basis of CDGP is poorly understood.
We characterized and compared the genetic architectures of CHH and CDGP, to test the hypothesis of a shared genetic basis between these disorders.
Exome sequencing data were used to identify rare variants in known genes in CHH ( <i>n</i>  = 116), CDGP ( <i>n</i>  = 72) and control cohorts ( <i>n</i>  = 36 874 ExAC and <i>n</i>  = 405 CoLaus).
Mutations in at least one CHH gene were found in 51% of CHH probands, which is significantly higher than in CDGP (7%, <i>P</i>  = 7.6 × 10 <sup>-11</sup> ) or controls (18%, <i>P</i>  = 5.5 × 10 <sup>-12</sup> ). Similarly, oligogenicity (defined as mutations in more than one gene) was common in CHH patients (15%) relative to CDGP (1.4%, <i>P</i>  = 0.002) and controls (2%, <i>P</i>  = 6.4 × 10 <sup>-7</sup> ).
Our data suggest that CDGP and CHH have distinct genetic profiles, and this finding may facilitate the differential diagnosis in patients presenting with delayed puberty.

Mots-clé
Adult, Aged, Cohort Studies, Female, Finland/epidemiology, Growth Disorders/diagnosis, Growth Disorders/epidemiology, Growth Disorders/genetics, Humans, Hypogonadism/diagnosis, Hypogonadism/epidemiology, Hypogonadism/genetics, Male, Middle Aged, Mutation/genetics, Puberty, Delayed/diagnosis, Puberty, Delayed/epidemiology, Puberty, Delayed/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/02/2018 21:12
Dernière modification de la notice
01/10/2019 14:51
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