2026-04-13T06:44:26Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/85032025-10-24T10:37:35Zcom_2072_378070com_2072_378040col_2072_378092

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 Fernández Álvarez, Paula Glàndules endocrines - Malalties - Diagnòstic Malalties congènites - Diagnòstic Enquestes DISEASES::Endocrine System Diseases Other subheadings::Other subheadings::/diagnosis ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Genetic Testing DISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Rare Diseases ENFERMEDADES::enfermedades del sistema endocrino Otros calificadores::Otros calificadores::/diagnóstico TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::técnicas y procedimientos diagnósticos::técnicas de laboratorio clínico::pruebas genéticas ENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::enfermedades raras Disorders of sex development; Next-generation sequencing; Primary ovarian insufficiency Trastornos del desarrollo sexual; Secuenciación de próxima generación; Insuficiencia ovárica primaria Trastorns del desenvolupament sexual; Seqüenciació de nova generació; Insuficiència ovàrica primària 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. This publication has been supported by Endo-ERN, which is co-funded by the European Union’s 3rd Health Programme (CHAFEA Framework Partnership Agreement No 739527). 2025-10-24T10:37:35Z 2025-10-24T10:37:35Z 2025-10-24T10:37:35Z 2022-11-18T13:26:40Z 2022-11-18T13:26:40Z 2022-11-14 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/8503 Endocrine Connections;11(12) https://doi.org/10.1530/EC-22-0367 Attribution-NonCommercial 4.0 International http://creativecommons.org/licenses/by-nc/4.0/ info:eu-repo/semantics/openAccess Bioscientifica Scientia