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

Cassatella, Daniele; Howard, Sasha R; Acierno, James S; Xu, Cheng; Papadakis, Georgios E; Santoni, Federico A; Dwyer, Andrew A; Santini, Sara; Sykiotis, Gerasimos P; Chambion, Caroline; Meylan, Jenny; Marino, Laura; Favre, Lucie; Li, Jiankang; Liu, Xuanzhu; Zhang, Jianguo; Bouloux, Pierre-Marc; Geyter, Christian De; Paepe, Anne De; Dhillo, Waljit S; ... (2018). Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures. European journal of endocrinology, 178(4), pp. 377-388. BioScientifica Ltd. 10.1530/EJE-17-0568

Preview

Text [1479683X - European Journal of Endocrinology] Congenital hypogonadotropic hypogonadism and constitutional delay of growth and puberty have distinct genetic architectures.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (1MB) | Preview

OBJECTIVE

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.

DESIGN

We characterized and compared the genetic architectures of CHH and CDGP, to test the hypothesis of a shared genetic basis between these disorders.

METHODS

Exome sequencing data were used to identify rare variants in known genes in CHH ( = 116), CDGP ( = 72) and control cohorts ( = 36 874 ExAC and  = 405 CoLaus).

RESULTS

Mutations in at least one CHH gene were found in 51% of CHH probands, which is significantly higher than in CDGP (7%,  = 7.6 × 10) or controls (18%,  = 5.5 × 10). Similarly, oligogenicity (defined as mutations in more than one gene) was common in CHH patients (15%) relative to CDGP (1.4%,  = 0.002) and controls (2%,  = 6.4 × 10).

CONCLUSIONS

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.

Interest & Impact

Downloads

209 since deposited on 26 Feb 2019
34 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item