Genetic and phenotypic differences between sexes in congenital hypogonadotropic hypogonadism (CHH): Large cohort analysis from a single tertiary centre.
GnRH (gonadotropin releasing hormone)
congenital hypogonadotropic hypogonadism (CHH)
female
genetics
phenotype [mesh]
sex
Journal
Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782
Informations de publication
Date de publication:
2022
2022
Historique:
received:
09
06
2022
accepted:
14
11
2022
entrez:
19
12
2022
pubmed:
20
12
2022
medline:
21
12
2022
Statut:
epublish
Résumé
Congenital hypogonadotropic hypogonadism (CHH) is a condition with a strong genetic background, caused by a deficient production, secretion, or action of gonadotropin-releasing hormone (GnRH). Published data on CHH cohorts indicate a male predominance, although this is not supported by our current understandings. In order to unravel the possible causes or contributors to such epidemiological sex difference, the aim of our study is to investigate differences in genetic background and clinical presentation between males and females in a large cohort of CHH patients. We enrolled 338 CHH patients with absent or arrested pubertal development, referred to our Center from 01/2016. Data collection included clinical assessment at diagnosis and genetic analysis performed by next generation sequencing (NGS), employing a custom panel of 28 candidate genes. Among 338 patients 94 were female (F) and 244 male (M), with a ratio of 1:2.6. We found that 36.09% (122/338) of patients harbored potentially pathogenic rare genetic variants (RVs) with no significant differences between sexes; on the other hand, a significantly higher frequency of oligogenicity was observed in females (F 9,57% 9/94 vs M 3,69% 9/244, Our data confirm the male predominance in CHH and identify some differences with regard to the clinical presentation between males and females that could indicate a variable expression of genetic rare variants and a dimorphic modulation of phenotype according to metabolic/behavioral factors, which will need to be substantiated and investigated by further studies.
Sections du résumé
Background
Congenital hypogonadotropic hypogonadism (CHH) is a condition with a strong genetic background, caused by a deficient production, secretion, or action of gonadotropin-releasing hormone (GnRH). Published data on CHH cohorts indicate a male predominance, although this is not supported by our current understandings.
Aims
In order to unravel the possible causes or contributors to such epidemiological sex difference, the aim of our study is to investigate differences in genetic background and clinical presentation between males and females in a large cohort of CHH patients.
Materials and methods
We enrolled 338 CHH patients with absent or arrested pubertal development, referred to our Center from 01/2016. Data collection included clinical assessment at diagnosis and genetic analysis performed by next generation sequencing (NGS), employing a custom panel of 28 candidate genes.
Results
Among 338 patients 94 were female (F) and 244 male (M), with a ratio of 1:2.6. We found that 36.09% (122/338) of patients harbored potentially pathogenic rare genetic variants (RVs) with no significant differences between sexes; on the other hand, a significantly higher frequency of oligogenicity was observed in females (F 9,57% 9/94 vs M 3,69% 9/244,
Conclusion
Our data confirm the male predominance in CHH and identify some differences with regard to the clinical presentation between males and females that could indicate a variable expression of genetic rare variants and a dimorphic modulation of phenotype according to metabolic/behavioral factors, which will need to be substantiated and investigated by further studies.
Identifiants
pubmed: 36531499
doi: 10.3389/fendo.2022.965074
pmc: PMC9755160
doi:
Substances chimiques
Gonadotropin-Releasing Hormone
33515-09-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
965074Informations de copyright
Copyright © 2022 Federici, Cangiano, Goggi, Messetti, Munari, Amer, Giovanelli, Hrvat, Vezzoli, Persani and Bonomi.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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