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

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 repres...

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Autores principales: Persani, Luca, Cools, Martine, Ioakim, Stamatina, Faisal Ahmed, S, Andonova, Silvia, Avbelj-Stefanija, Magdalena, Baronio, Federico, Bouligand, Jerome, Bruggenwirth, Hennie T, Davies, Justin H, De Baere, Elfride, Dzivite-Krisane, Iveta, Fernandez-Alvarez, Paula, Gheldof, Alexander, Giavoli, Claudia, Gravholt, Claus H, Hiort, Olaf, Holterhus, Paul-Martin, Juul, Anders, Krausz, Csilla, Lagerstedt-Robinson, Kristina, McGowan, Ruth, Neumann, Uta, Novelli, Antonio, Peyrassol, Xavier, Phylactou, Leonidas A, Rohayem, Julia, Touraine, Philippe, Westra, Dineke, Vezzoli, Valeria, Rossetti, Raffaella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9716404/
https://www.ncbi.nlm.nih.gov/pubmed/36228316
http://dx.doi.org/10.1530/EC-22-0367
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author Persani, Luca
Cools, Martine
Ioakim, Stamatina
Faisal Ahmed, S
Andonova, Silvia
Avbelj-Stefanija, Magdalena
Baronio, Federico
Bouligand, Jerome
Bruggenwirth, Hennie T
Davies, Justin H
De Baere, Elfride
Dzivite-Krisane, Iveta
Fernandez-Alvarez, Paula
Gheldof, Alexander
Giavoli, Claudia
Gravholt, Claus H
Hiort, Olaf
Holterhus, Paul-Martin
Juul, Anders
Krausz, Csilla
Lagerstedt-Robinson, Kristina
McGowan, Ruth
Neumann, Uta
Novelli, Antonio
Peyrassol, Xavier
Phylactou, Leonidas A
Rohayem, Julia
Touraine, Philippe
Westra, Dineke
Vezzoli, Valeria
Rossetti, Raffaella
author_facet Persani, Luca
Cools, Martine
Ioakim, Stamatina
Faisal Ahmed, S
Andonova, Silvia
Avbelj-Stefanija, Magdalena
Baronio, Federico
Bouligand, Jerome
Bruggenwirth, Hennie T
Davies, Justin H
De Baere, Elfride
Dzivite-Krisane, Iveta
Fernandez-Alvarez, Paula
Gheldof, Alexander
Giavoli, Claudia
Gravholt, Claus H
Hiort, Olaf
Holterhus, Paul-Martin
Juul, Anders
Krausz, Csilla
Lagerstedt-Robinson, Kristina
McGowan, Ruth
Neumann, Uta
Novelli, Antonio
Peyrassol, Xavier
Phylactou, Leonidas A
Rohayem, Julia
Touraine, Philippe
Westra, Dineke
Vezzoli, Valeria
Rossetti, Raffaella
author_sort Persani, Luca
collection PubMed
description 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.
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spelling pubmed-97164042022-12-06 The genetic diagnosis of rare endocrine disorders of sex development and maturation: a survey among Endo-ERN centres Persani, Luca Cools, Martine Ioakim, Stamatina Faisal Ahmed, S Andonova, Silvia Avbelj-Stefanija, Magdalena Baronio, Federico Bouligand, Jerome Bruggenwirth, Hennie T Davies, Justin H De Baere, Elfride Dzivite-Krisane, Iveta Fernandez-Alvarez, Paula Gheldof, Alexander Giavoli, Claudia Gravholt, Claus H Hiort, Olaf Holterhus, Paul-Martin Juul, Anders Krausz, Csilla Lagerstedt-Robinson, Kristina McGowan, Ruth Neumann, Uta Novelli, Antonio Peyrassol, Xavier Phylactou, Leonidas A Rohayem, Julia Touraine, Philippe Westra, Dineke Vezzoli, Valeria Rossetti, Raffaella Endocr Connect Research 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. Bioscientifica Ltd 2022-10-13 /pmc/articles/PMC9716404/ /pubmed/36228316 http://dx.doi.org/10.1530/EC-22-0367 Text en © The authors https://creativecommons.org/licenses/by-nc/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. (https://creativecommons.org/licenses/by-nc/4.0/)
spellingShingle Research
Persani, Luca
Cools, Martine
Ioakim, Stamatina
Faisal Ahmed, S
Andonova, Silvia
Avbelj-Stefanija, Magdalena
Baronio, Federico
Bouligand, Jerome
Bruggenwirth, Hennie T
Davies, Justin H
De Baere, Elfride
Dzivite-Krisane, Iveta
Fernandez-Alvarez, Paula
Gheldof, Alexander
Giavoli, Claudia
Gravholt, Claus H
Hiort, Olaf
Holterhus, Paul-Martin
Juul, Anders
Krausz, Csilla
Lagerstedt-Robinson, Kristina
McGowan, Ruth
Neumann, Uta
Novelli, Antonio
Peyrassol, Xavier
Phylactou, Leonidas A
Rohayem, Julia
Touraine, Philippe
Westra, Dineke
Vezzoli, Valeria
Rossetti, Raffaella
The genetic diagnosis of rare endocrine disorders of sex development and maturation: a survey among Endo-ERN centres
title The genetic diagnosis of rare endocrine disorders of sex development and maturation: a survey among Endo-ERN centres
title_full The genetic diagnosis of rare endocrine disorders of sex development and maturation: a survey among Endo-ERN centres
title_fullStr The genetic diagnosis of rare endocrine disorders of sex development and maturation: a survey among Endo-ERN centres
title_full_unstemmed The genetic diagnosis of rare endocrine disorders of sex development and maturation: a survey among Endo-ERN centres
title_short The genetic diagnosis of rare endocrine disorders of sex development and maturation: a survey among Endo-ERN centres
title_sort genetic diagnosis of rare endocrine disorders of sex development and maturation: a survey among endo-ern centres
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9716404/
https://www.ncbi.nlm.nih.gov/pubmed/36228316
http://dx.doi.org/10.1530/EC-22-0367
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