High precision characterization of RCCX rearrangements in a 21-hydroxylase deficiency Latin American cohort using oxford nanopore long read sequencing
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 amp...
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| Format: | info:ar-repo/semantics/artículo |
| Language: | Inglés |
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Springer Nature
2025
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| Online Access: | 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 |
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| author | 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_browse | Castro, Tania Claps, Aldana Dain, Liliana Delea, Marisol Fernandez, Franco Daniel Fernández, Cecilia Ingravidi, Marina L. Kamenetzky, Laura Laiseca, Julieta Macchiaroli, Natalia Taboas, Melisa |
| author_facet | 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_sort | Claps, Aldana |
| collection | INTA Digital |
| 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. |
| format | info:ar-repo/semantics/artículo |
| id | INTA23066 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | Springer Nature |
| publisherStr | Springer Nature |
| record_format | dspace |
| spelling | INTA230662025-07-17T14:49:48Z High precision characterization of RCCX rearrangements in a 21-hydroxylase deficiency Latin American cohort using oxford nanopore long read sequencing 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 Secuenciación por Nanoporos Genética Nanopore Sequencing Genetics RCCX Modules CYP21A2 Long Read Sequencing 21-hydroxylase Deficiency 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 2025-07-17T14:43:25Z 2025-07-17T14:43:25Z 2025-07-10 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 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 eng 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) application/pdf Springer Nature Scientific Reports 15 : 24983 (July 2025) |
| spellingShingle | Secuenciación por Nanoporos Genética Nanopore Sequencing Genetics RCCX Modules CYP21A2 Long Read Sequencing 21-hydroxylase Deficiency 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 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 |
| 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_short | 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 |
| topic | Secuenciación por Nanoporos Genética Nanopore Sequencing Genetics RCCX Modules CYP21A2 Long Read Sequencing 21-hydroxylase Deficiency |
| 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 |
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