Monogenic Forms of DSD: An Update.
Disorders/differences of sex development
Gonadal dysgenesis
Monogenic disorders
Journal
Hormone research in paediatrics
ISSN: 1663-2826
Titre abrégé: Horm Res Paediatr
Pays: Switzerland
ID NLM: 101525157
Informations de publication
Date de publication:
2023
2023
Historique:
received:
02
09
2021
accepted:
18
11
2021
medline:
1
6
2023
pubmed:
29
12
2021
entrez:
28
12
2021
Statut:
ppublish
Résumé
DSD encompass a wide range of pathologies that impact gonad formation, development, and function in both 46,XX and 46,XY individuals. The majority of these conditions are considered to be monogenic, although the expression of the phenotype may be influenced by genetic modifiers. Although considered monogenic, establishing the genetic etiology in DSD has been difficult compared to other congenital disorders for a number of reasons including the absence of family cases for classical genetic association studies and the lack of evolutionary conservation of key genetic factors involved in gonad formation. In recent years, the widespread use of genomic sequencing technologies has resulted in multiple genes being identified and proposed as novel monogenic causes of 46,XX and/or 46,XY DSD. In this review, we will focus on the main genomic findings of recent years, which consists of new candidate genes or loci for DSD as well as new reproductive phenotypes associated with genes that are well established to cause DSD. For each gene or loci, we summarize the data that are currently available in favor of or against a role for these genes in DSD or the contribution of genomic variants within well-established genes to a new reproductive phenotype. Based on this analysis, we propose a series of recommendations that should aid the interpretation of genomic data and ultimately help to improve the accuracy and yield genetic diagnosis of DSD.
Sections du résumé
BACKGROUND
BACKGROUND
DSD encompass a wide range of pathologies that impact gonad formation, development, and function in both 46,XX and 46,XY individuals. The majority of these conditions are considered to be monogenic, although the expression of the phenotype may be influenced by genetic modifiers. Although considered monogenic, establishing the genetic etiology in DSD has been difficult compared to other congenital disorders for a number of reasons including the absence of family cases for classical genetic association studies and the lack of evolutionary conservation of key genetic factors involved in gonad formation. In recent years, the widespread use of genomic sequencing technologies has resulted in multiple genes being identified and proposed as novel monogenic causes of 46,XX and/or 46,XY DSD.
SUMMARY
CONCLUSIONS
In this review, we will focus on the main genomic findings of recent years, which consists of new candidate genes or loci for DSD as well as new reproductive phenotypes associated with genes that are well established to cause DSD. For each gene or loci, we summarize the data that are currently available in favor of or against a role for these genes in DSD or the contribution of genomic variants within well-established genes to a new reproductive phenotype.
KEY MESSAGES
CONCLUSIONS
Based on this analysis, we propose a series of recommendations that should aid the interpretation of genomic data and ultimately help to improve the accuracy and yield genetic diagnosis of DSD.
Identifiants
pubmed: 34963118
pii: 000521381
doi: 10.1159/000521381
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
144-168Informations de copyright
© 2021 The Author(s). Published by S. Karger AG, Basel.