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The genetic diagnosis of rare endocrine disorders of sex development and maturation: a survey among Endo-ERN centres

Authors :
Luca Persani
Martine Cools
Stamatina Ioakim
S Faisal Ahmed
Silvia Andonova
Magdalena Avbelj-Stefanija
Federico Baronio
Jerome Bouligand
Hennie T Bruggenwirth
Justin H Davies
Elfride De Baere
Iveta Dzivite-Krisane
Paula Fernandez-Alvarez
Alexander Gheldof
Claudia Giavoli
Claus H Gravholt
Olaf Hiort
Paul-Martin Holterhus
Anders Juul
Csilla Krausz
Kristina Lagerstedt-Robinson
Ruth McGowan
Uta Neumann
Antonio Novelli
Xavier Peyrassol
Leonidas A Phylactou
Julia Rohayem
Philippe Touraine
Dineke Westra
Valeria Vezzoli
Raffaella Rossetti
Source :
Endocrine Connections, Vol 11, Iss 22, Pp 1-7 (2022)
Publication Year :
2022
Publisher :
Bioscientifica, 2022.

Abstract

Differences of sex development and maturation (SDM) represent a heterogeneous puzzle of rare conditions with a large genetic component whose management and treatment could be improved by an accurate classification of underlying molecular conditions, and next-generation sequencing (NGS) should represent the most appropriate approach. Therefore, we conducted a survey dedicated to the use and potential outcomes of NGS for SDM disorders diagnosis among the 53 health care providers (HCP) of the European Reference Network for rare endocrine conditions. The response rate was 49% with a total of 26 HCPs from 13 countries. All HCPs, except 1, performed NGS investigations for SDM disorders on 6720 patients, 3764 (56%) with differences of sex development (DSD), including 811 unexplained primary ovarian insufficiency, and 2956 (44%) with congenital hypogonadotropic hypogonadism (CHH). The approaches varied from targeted analysis of custom gene panels (range: 11–490 genes) in 81.5% of cases or whole exome sequencing with the extraction of a virtual panel in the remaining cases. These analyses were performed for diagnostic purposes in 21 HCPs, supported by the National Health Systems in 16 cases. The likelihood of finding a variant ranged between 7 and 60%, mainly depending upon the number of analysed genes or criteria used for reporting, most HCPs also reporting variants of uncertain significance. These data illustrate the status of genetic diagnosis of DSD and CHH across Europe. In most countries, these analyses are performed for diagnostic purposes, yielding highly variable results, thus suggesting the need for harmonization and general improvements of NGS approaches.

Details

Language :
English
ISSN :
20493614
Volume :
11
Issue :
22
Database :
Directory of Open Access Journals
Journal :
Endocrine Connections
Publication Type :
Academic Journal
Accession number :
edsdoj.2d8fa80d5d96414aaaa8f97a72aee4ac
Document Type :
article
Full Text :
https://doi.org/10.1530/EC-22-0367