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

[img]
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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine

UniBE Contributor:

Flück Pandey, Christa Emma

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0804-4643

Publisher:

BioScientifica Ltd.

Language:

English

Submitter:

Christa Emma Flück Pandey

Date Deposited:

26 Feb 2019 14:31

Last Modified:

01 Nov 2019 06:15

Publisher DOI:

10.1530/EJE-17-0568

PubMed ID:

29419413

BORIS DOI:

10.7892/boris.123702

URI:

https://boris.unibe.ch/id/eprint/123702

Actions (login required)

Edit item Edit item
Provide Feedback