High precision characterization of RCCX rearrangements in a 21-hydroxylase deficiency Latin American cohort using oxford nanopore long read sequencing

Autores
Claps, Aldana; Fernández, Cecilia; Fernandez, Franco Daniel; Macchiaroli, Natalia; Ingravidi, Marina L.; Delea, Marisol; Fernández, Cecilia; Castro, Tania; Laiseca, Julieta; Kamenetzky, Laura; Taboas, Melisa; Dain, Liliana
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The CYP21A2 gene, mapped to the RCCX module in 6p21.3, is responsible for 21-hydroxylase deficiency (21-HD). In this work, we leveraged Oxford Nanopore Technology (ONT) Long Read sequencing (LRS) to analyze samples from an Argentinian cohort of 21-HD. A total of 34 samples were sequenced in 2 amplicons of 8.5 Kb covering the centromeric and telomeric RCCX modules. The number of variants found varied between 3 and 106 and all expected pathogenic variants and new ones were obtained with the LR sequencing workflow developed. We defined with higher accuracy the breakpoints of the rearrangements allowing the reclassification of chimeras and/or converted genes in 18.75% of the samples, some of them with clinical implications. By addressing the study of the telomeric RCCX module/s in depth, we found 19 genetic variants (GVs) for CYP21A1P and 29 GVs for TNXA not previously described in Latin American populations. This study may represent the first application of ONT LRS for clinical evaluation of Latin American subjects, highlighting the importance of LRS as a high-resolution method of diagnosis. It would allow a better understanding of the diversity of the RCCX modules and improve our knowledge of the variation of genetic mechanisms behind the disease.
Instituto de Patología Vegetal
Fil: Claps, Aldana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Centro Nacional de Genética Médica; Argentina
Fil: Fernández, Cecilia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3); Argentina
Fil: Fernandez, Franco Daniel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; Argentina
Fil: Fernandez, Franco Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Fitopatología y Modelización Agrícola (UFyMA); Argentina
Fil: Macchiaroli, Natalia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3); Argentina
Fil: Ingravidi, Marina L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3); Argentina
Fil: Delea, Marisol. Hospital de Alta Complejidad El Calafate SAMIC. Unidad de Conocimiento Traslacional Hospitalaria Patagónica; Argentina
Fil: Fernández, Cecilia. Laboratorio Novagen; Argentina
Fil: Castro, Tania. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos G Malbrán”. Centro Nacional de Genética Médica; Argentina
Fil: Laiseca, Julieta. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos G Malbrán”. Centro Nacional de Genética Médica; Argentina
Fil: Kamenetzky, Laura. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3); Argentina
Fil: Taboas, Melisa. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos G Malbrán”. Centro Nacional de Genética Médica; Argentina
Fil: Dain, Liliana. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos G Malbrán. Centro Nacional de Genética Médica; Argentina
Fil: Dain, Liliana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3); Argentina
Fuente
Scientific Reports 15 : 24983 (July 2025)
Materia
Secuenciación por Nanoporos
Genética
Nanopore Sequencing
Genetics
RCCX Modules
CYP21A2
Long Read Sequencing
21-hydroxylase Deficiency
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
INTA Digital (INTA)
Institución
Instituto Nacional de Tecnología Agropecuaria
OAI Identificador
oai:localhost:20.500.12123/23066
Acceder
id INTADig_51665a89f2727a0fbcb3ea24a8697186
oai_identifier_str oai:localhost:20.500.12123/23066
network_acronym_str INTADig
repository_id_str l
network_name_str INTA Digital (INTA)
spelling High precision characterization of RCCX rearrangements in a 21-hydroxylase deficiency Latin American cohort using oxford nanopore long read sequencingClaps, AldanaFernández, CeciliaFernandez, Franco DanielMacchiaroli, NataliaIngravidi, Marina L.Delea, MarisolFernández, CeciliaCastro, TaniaLaiseca, JulietaKamenetzky, LauraTaboas, MelisaDain, LilianaSecuenciación por NanoporosGenéticaNanopore SequencingGeneticsRCCX ModulesCYP21A2Long Read Sequencing21-hydroxylase DeficiencyThe CYP21A2 gene, mapped to the RCCX module in 6p21.3, is responsible for 21-hydroxylase deficiency (21-HD). In this work, we leveraged Oxford Nanopore Technology (ONT) Long Read sequencing (LRS) to analyze samples from an Argentinian cohort of 21-HD. A total of 34 samples were sequenced in 2 amplicons of 8.5 Kb covering the centromeric and telomeric RCCX modules. The number of variants found varied between 3 and 106 and all expected pathogenic variants and new ones were obtained with the LR sequencing workflow developed. We defined with higher accuracy the breakpoints of the rearrangements allowing the reclassification of chimeras and/or converted genes in 18.75% of the samples, some of them with clinical implications. By addressing the study of the telomeric RCCX module/s in depth, we found 19 genetic variants (GVs) for CYP21A1P and 29 GVs for TNXA not previously described in Latin American populations. This study may represent the first application of ONT LRS for clinical evaluation of Latin American subjects, highlighting the importance of LRS as a high-resolution method of diagnosis. It would allow a better understanding of the diversity of the RCCX modules and improve our knowledge of the variation of genetic mechanisms behind the disease.Instituto de Patología VegetalFil: Claps, Aldana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Centro Nacional de Genética Médica; ArgentinaFil: Fernández, Cecilia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3); ArgentinaFil: Fernandez, Franco Daniel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; ArgentinaFil: Fernandez, Franco Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Fitopatología y Modelización Agrícola (UFyMA); ArgentinaFil: Macchiaroli, Natalia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3); ArgentinaFil: Ingravidi, Marina L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3); ArgentinaFil: Delea, Marisol. Hospital de Alta Complejidad El Calafate SAMIC. Unidad de Conocimiento Traslacional Hospitalaria Patagónica; ArgentinaFil: Fernández, Cecilia. Laboratorio Novagen; ArgentinaFil: Castro, Tania. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos G Malbrán”. Centro Nacional de Genética Médica; ArgentinaFil: Laiseca, Julieta. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos G Malbrán”. Centro Nacional de Genética Médica; ArgentinaFil: Kamenetzky, Laura. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3); ArgentinaFil: Taboas, Melisa. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos G Malbrán”. Centro Nacional de Genética Médica; ArgentinaFil: Dain, Liliana. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos G Malbrán. Centro Nacional de Genética Médica; ArgentinaFil: Dain, Liliana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3); ArgentinaSpringer Nature2025-07-17T14:43:25Z2025-07-17T14:43:25Z2025-07-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12123/23066https://www.nature.com/articles/s41598-025-03799-72045-2322https://doi.org/10.1038/s41598-025-03799-7Scientific Reports 15 : 24983 (July 2025)reponame:INTA Digital (INTA)instname:Instituto Nacional de Tecnología Agropecuariaenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)2025-09-04T09:51:11Zoai:localhost:20.500.12123/23066instacron:INTAInstitucionalhttp://repositorio.inta.gob.ar/Organismo científico-tecnológicoNo correspondehttp://repositorio.inta.gob.ar/oai/requesttripaldi.nicolas@inta.gob.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:l2025-09-04 09:51:11.822INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuariafalse
dc.title.none.fl_str_mv High precision characterization of RCCX rearrangements in a 21-hydroxylase deficiency Latin American cohort using oxford nanopore long read sequencing
title High precision characterization of RCCX rearrangements in a 21-hydroxylase deficiency Latin American cohort using oxford nanopore long read sequencing
spellingShingle High precision characterization of RCCX rearrangements in a 21-hydroxylase deficiency Latin American cohort using oxford nanopore long read sequencing
Claps, Aldana
Secuenciación por Nanoporos
Genética
Nanopore Sequencing
Genetics
RCCX Modules
CYP21A2
Long Read Sequencing
21-hydroxylase Deficiency
title_short High precision characterization of RCCX rearrangements in a 21-hydroxylase deficiency Latin American cohort using oxford nanopore long read sequencing
title_full High precision characterization of RCCX rearrangements in a 21-hydroxylase deficiency Latin American cohort using oxford nanopore long read sequencing
title_fullStr High precision characterization of RCCX rearrangements in a 21-hydroxylase deficiency Latin American cohort using oxford nanopore long read sequencing
title_full_unstemmed High precision characterization of RCCX rearrangements in a 21-hydroxylase deficiency Latin American cohort using oxford nanopore long read sequencing
title_sort High precision characterization of RCCX rearrangements in a 21-hydroxylase deficiency Latin American cohort using oxford nanopore long read sequencing
dc.creator.none.fl_str_mv Claps, Aldana
Fernández, Cecilia
Fernandez, Franco Daniel
Macchiaroli, Natalia
Ingravidi, Marina L.
Delea, Marisol
Fernández, Cecilia
Castro, Tania
Laiseca, Julieta
Kamenetzky, Laura
Taboas, Melisa
Dain, Liliana
author Claps, Aldana
author_facet Claps, Aldana
Fernández, Cecilia
Fernandez, Franco Daniel
Macchiaroli, Natalia
Ingravidi, Marina L.
Delea, Marisol
Castro, Tania
Laiseca, Julieta
Kamenetzky, Laura
Taboas, Melisa
Dain, Liliana
author_role author
author2 Fernández, Cecilia
Fernandez, Franco Daniel
Macchiaroli, Natalia
Ingravidi, Marina L.
Delea, Marisol
Castro, Tania
Laiseca, Julieta
Kamenetzky, Laura
Taboas, Melisa
Dain, Liliana
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Secuenciación por Nanoporos
Genética
Nanopore Sequencing
Genetics
RCCX Modules
CYP21A2
Long Read Sequencing
21-hydroxylase Deficiency
topic Secuenciación por Nanoporos
Genética
Nanopore Sequencing
Genetics
RCCX Modules
CYP21A2
Long Read Sequencing
21-hydroxylase Deficiency
dc.description.none.fl_txt_mv The CYP21A2 gene, mapped to the RCCX module in 6p21.3, is responsible for 21-hydroxylase deficiency (21-HD). In this work, we leveraged Oxford Nanopore Technology (ONT) Long Read sequencing (LRS) to analyze samples from an Argentinian cohort of 21-HD. A total of 34 samples were sequenced in 2 amplicons of 8.5 Kb covering the centromeric and telomeric RCCX modules. The number of variants found varied between 3 and 106 and all expected pathogenic variants and new ones were obtained with the LR sequencing workflow developed. We defined with higher accuracy the breakpoints of the rearrangements allowing the reclassification of chimeras and/or converted genes in 18.75% of the samples, some of them with clinical implications. By addressing the study of the telomeric RCCX module/s in depth, we found 19 genetic variants (GVs) for CYP21A1P and 29 GVs for TNXA not previously described in Latin American populations. This study may represent the first application of ONT LRS for clinical evaluation of Latin American subjects, highlighting the importance of LRS as a high-resolution method of diagnosis. It would allow a better understanding of the diversity of the RCCX modules and improve our knowledge of the variation of genetic mechanisms behind the disease.
Instituto de Patología Vegetal
Fil: Claps, Aldana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán". Centro Nacional de Genética Médica; Argentina
Fil: Fernández, Cecilia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3); Argentina
Fil: Fernandez, Franco Daniel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patología Vegetal; Argentina
Fil: Fernandez, Franco Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Fitopatología y Modelización Agrícola (UFyMA); Argentina
Fil: Macchiaroli, Natalia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3); Argentina
Fil: Ingravidi, Marina L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3); Argentina
Fil: Delea, Marisol. Hospital de Alta Complejidad El Calafate SAMIC. Unidad de Conocimiento Traslacional Hospitalaria Patagónica; Argentina
Fil: Fernández, Cecilia. Laboratorio Novagen; Argentina
Fil: Castro, Tania. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos G Malbrán”. Centro Nacional de Genética Médica; Argentina
Fil: Laiseca, Julieta. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos G Malbrán”. Centro Nacional de Genética Médica; Argentina
Fil: Kamenetzky, Laura. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3); Argentina
Fil: Taboas, Melisa. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos G Malbrán”. Centro Nacional de Genética Médica; Argentina
Fil: Dain, Liliana. Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) “Dr. Carlos G Malbrán. Centro Nacional de Genética Médica; Argentina
Fil: Dain, Liliana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3); Argentina
description The CYP21A2 gene, mapped to the RCCX module in 6p21.3, is responsible for 21-hydroxylase deficiency (21-HD). In this work, we leveraged Oxford Nanopore Technology (ONT) Long Read sequencing (LRS) to analyze samples from an Argentinian cohort of 21-HD. A total of 34 samples were sequenced in 2 amplicons of 8.5 Kb covering the centromeric and telomeric RCCX modules. The number of variants found varied between 3 and 106 and all expected pathogenic variants and new ones were obtained with the LR sequencing workflow developed. We defined with higher accuracy the breakpoints of the rearrangements allowing the reclassification of chimeras and/or converted genes in 18.75% of the samples, some of them with clinical implications. By addressing the study of the telomeric RCCX module/s in depth, we found 19 genetic variants (GVs) for CYP21A1P and 29 GVs for TNXA not previously described in Latin American populations. This study may represent the first application of ONT LRS for clinical evaluation of Latin American subjects, highlighting the importance of LRS as a high-resolution method of diagnosis. It would allow a better understanding of the diversity of the RCCX modules and improve our knowledge of the variation of genetic mechanisms behind the disease.
publishDate 2025
dc.date.none.fl_str_mv 2025-07-17T14:43:25Z
2025-07-17T14:43:25Z
2025-07-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12123/23066
https://www.nature.com/articles/s41598-025-03799-7
2045-2322
https://doi.org/10.1038/s41598-025-03799-7
url http://hdl.handle.net/20.500.12123/23066
https://www.nature.com/articles/s41598-025-03799-7
https://doi.org/10.1038/s41598-025-03799-7
identifier_str_mv 2045-2322
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv Scientific Reports 15 : 24983 (July 2025)
reponame:INTA Digital (INTA)
instname:Instituto Nacional de Tecnología Agropecuaria
reponame_str INTA Digital (INTA)
collection INTA Digital (INTA)
instname_str Instituto Nacional de Tecnología Agropecuaria
repository.name.fl_str_mv INTA Digital (INTA) - Instituto Nacional de Tecnología Agropecuaria
repository.mail.fl_str_mv tripaldi.nicolas@inta.gob.ar
_version_ 1842341442738978816
score 12.623145

Publicaciones similares