Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy
The SPATA5 gene encodes a 892 amino-acids long protein that has a putative mitochondrial targeting sequence and has been proposed to function in maintenance of mitochondrial function and integrity during mouse spermatogenesis. Several studies have associated homozygous or compound heterozygous mutat...
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| Format: | article |
| Idioma: | anglès |
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2023
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| Accés en línia: | https://hdl.handle.net/20.500.12008/53861 |
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| _version_ | 1868890127665725440 |
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| author | Raggio, Víctor |
| author2 | Graña, Martín Winiarski, Erik Mansilla, Santiago Simoes, Camila Rodríguez, Soledad Brandes, Mariana Tapié, Alejandra Rodríguez, Laura Cibils, Lucía Alonso, Martina Martínez, Jennyfer Fernández-Calero, Tamara Domínguez, Fernanda Rosas Mezquida, Melania Castro, Laura Cerisola, Alfredo Naya, Hugo Cassina, Adriana Quijano, Celia Spangenberg, Lucía |
| author2_role | author author author author author author author author author author author author author author author author author author author author |
| author_browse | Alonso, Martina Brandes, Mariana Cassina, Adriana Castro, Laura Cerisola, Alfredo Cibils, Lucía Domínguez, Fernanda Fernández-Calero, Tamara Graña, Martín Mansilla, Santiago Martínez, Jennyfer Naya, Hugo Quijano, Celia Raggio, Víctor Rodríguez, Laura Rodríguez, Soledad Rosas Mezquida, Melania Simoes, Camila Spangenberg, Lucía Tapié, Alejandra Winiarski, Erik |
| author_facet | Raggio, Víctor Graña, Martín Winiarski, Erik Mansilla, Santiago Simoes, Camila Rodríguez, Soledad Brandes, Mariana Tapié, Alejandra Rodríguez, Laura Cibils, Lucía Alonso, Martina Martínez, Jennyfer Fernández-Calero, Tamara Domínguez, Fernanda Rosas Mezquida, Melania Castro, Laura Cerisola, Alfredo Naya, Hugo Cassina, Adriana Quijano, Celia Spangenberg, Lucía |
| author_role | author |
| collection | COLIBRI |
| dc.contributor.none.fl_str_mv | Raggio Víctor, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Genética Graña Martín, Institut Pasteur de Montevideo (Uruguay). Unidad de Bioinformática Winiarski Erik, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Histología y Embriología Mansilla Santiago, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Métodos Cuantitativos Simoes Camila, Universidad de la República (Uruguay). Facultad de Medicina. Departamento Básico de Medicina Rodríguez Soledad, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Genética Brandes Mariana, Institut Pasteur de Montevideo (Uruguay). Unidad de Bioinformática Tapié Alejandra, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Genética Rodríguez Laura, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Genética Cibils Lucía, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Neuropediatría Alonso Martina, Universidad de la República (Uruguay). Facultad de Medicina. Centro de Investigaciones Biomédicas (CEINBIO) Martínez Jennyfer, Universidad de la República (Uruguay). Facultad de Medicina. Centro de Investigaciones Biomédicas (CEINBIO) Fernández-Calero Tamara, Universidad Católica del Uruguay (Uruguay). Departamento de Ciencias Exactas y Naturales Domínguez Fernanda, Universidad Católica del Uruguay (Uruguay) Rosas Mezquida Melania, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Neuropediatría Castro Laura, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Bioquímica Cerisola Alfredo, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Neuropediatría Naya Hugo, Universidad de la República (Uruguay). Facultad de Agronomía. Departamento de Producción Animal y Pasturas Cassina Adriana, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Bioquímica Quijano Celia, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Bioquímica Spangenberg Lucía, Universidad de la República (Uruguay). Facultad de Medicina. Departamento Básico de Medicina |
| dc.creator.none.fl_str_mv | Raggio, Víctor Graña, Martín Winiarski, Erik Mansilla, Santiago Simoes, Camila Rodríguez, Soledad Brandes, Mariana Tapié, Alejandra Rodríguez, Laura Cibils, Lucía Alonso, Martina Martínez, Jennyfer Fernández-Calero, Tamara Domínguez, Fernanda Rosas Mezquida, Melania Castro, Laura Cerisola, Alfredo Naya, Hugo Cassina, Adriana Quijano, Celia Spangenberg, Lucía |
| dc.date.none.fl_str_mv | 2023 2026-03-13T15:03:50Z 2026-03-13T15:03:50Z |
| dc.format.none.fl_str_mv | 13 p. application/pdf |
| dc.identifier.none.fl_str_mv | Raggio V, Graña M, Winiarski E y otros. Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy. Human Genomics [en línea]. 2023;17(1). 13 p. https://hdl.handle.net/20.500.12008/53861 10.1186/s40246-023-00463-x 1479-7364 |
| dc.language.none.fl_str_mv | en eng |
| dc.publisher.none.fl_str_mv | Springer Nature |
| dc.relation.none.fl_str_mv | Human Genomics. 2023;17(1) |
| dc.rights.none.fl_str_mv | info:eu-repo/semantics/openAccess Licencia Creative Commons Atribución (CC - By 4.0) |
| dc.source.none.fl_str_mv | reponame:COLIBRI instname:Universidad de la República instacron:Universidad de la República |
| dc.subject.none.fl_str_mv | ATPasas ASOCIADAS CON ACTIVIDADES CELULARES DIVERSAS METABOLISMO ANIMALES BIOPSIA ENCEFALOPATÍAS RATONES MASCULINO MICROCEFALIA MITOCONDRIAS CONVULSIONES GENÉTICA |
| dc.title.none.fl_str_mv | Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy |
| dc.type.none.fl_str_mv | Artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| description | The SPATA5 gene encodes a 892 amino-acids long protein that has a putative mitochondrial targeting sequence and has been proposed to function in maintenance of mitochondrial function and integrity during mouse spermatogenesis. Several studies have associated homozygous or compound heterozygous mutations in SPATA5 gene to microcephaly, intellectual disability, seizures and hearing loss. This suggests a role of the SPATA5 gene also in neuronal development. Recently, our group presented results validating the use of blood cells for the assessment of mitochondrial function for diagnosis and follow-up of mitochondrial disease, minimizing the need for invasive procedures such as muscle biopsy. In this study, we were able to diagnose a patient with epileptogenic encephalopathy using next generation sequencing. We found two novel compound heterozygous variants in SPATA5 that are most likely causative. To analyze the impact of SPATA5 mutations on mitochondrial functional studies directly on the patients’ mononuclear cells and platelets were undertaken. Oxygen consumption rates in platelets and PBMCs were impaired in the patient when compared to a healthy control. Also, a decrease in mitochondrial mass was observed in the patient monocytes with respect to the control. This suggests a true pathogenic effect of the mutations in mitochondrial function, especially in energy production and possibly biogenesis, leading to the observed phenotype. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | anni_8d3e28c4a58fdb2afecfba1ea8a5c95a |
| identifier_str_mv | Raggio V, Graña M, Winiarski E y otros. Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy. Human Genomics [en línea]. 2023;17(1). 13 p. 10.1186/s40246-023-00463-x 1479-7364 |
| instacron_str | Universidad de la República |
| institution | Universidad de la República |
| instname_str | Universidad de la República |
| language | eng |
| language_invalid_str_mv | en |
| network_acronym_str | anni |
| network_name_str | oai-lr-anni |
| oai_identifier_str | oai:colibri.udelar.edu.uy:20.500.12008/53861 |
| publishDate | 2023 |
| publishDateSort | 2023 |
| publisher.none.fl_str_mv | Springer Nature |
| reponame_str | COLIBRI |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | Licencia Creative Commons Atribución (CC - By 4.0) |
| spelling | Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathyRaggio, VíctorGraña, MartínWiniarski, ErikMansilla, SantiagoSimoes, CamilaRodríguez, SoledadBrandes, MarianaTapié, AlejandraRodríguez, LauraCibils, LucíaAlonso, MartinaMartínez, JennyferFernández-Calero, TamaraDomínguez, FernandaRosas Mezquida, MelaniaCastro, LauraCerisola, AlfredoNaya, HugoCassina, AdrianaQuijano, CeliaSpangenberg, LucíaATPasas ASOCIADAS CON ACTIVIDADES CELULARES DIVERSASMETABOLISMOANIMALESBIOPSIAENCEFALOPATÍASRATONESMASCULINOMICROCEFALIAMITOCONDRIASCONVULSIONESGENÉTICAThe SPATA5 gene encodes a 892 amino-acids long protein that has a putative mitochondrial targeting sequence and has been proposed to function in maintenance of mitochondrial function and integrity during mouse spermatogenesis. Several studies have associated homozygous or compound heterozygous mutations in SPATA5 gene to microcephaly, intellectual disability, seizures and hearing loss. This suggests a role of the SPATA5 gene also in neuronal development. Recently, our group presented results validating the use of blood cells for the assessment of mitochondrial function for diagnosis and follow-up of mitochondrial disease, minimizing the need for invasive procedures such as muscle biopsy. In this study, we were able to diagnose a patient with epileptogenic encephalopathy using next generation sequencing. We found two novel compound heterozygous variants in SPATA5 that are most likely causative. To analyze the impact of SPATA5 mutations on mitochondrial functional studies directly on the patients’ mononuclear cells and platelets were undertaken. Oxygen consumption rates in platelets and PBMCs were impaired in the patient when compared to a healthy control. Also, a decrease in mitochondrial mass was observed in the patient monocytes with respect to the control. This suggests a true pathogenic effect of the mutations in mitochondrial function, especially in energy production and possibly biogenesis, leading to the observed phenotype.Springer NatureRaggio Víctor, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de GenéticaGraña Martín, Institut Pasteur de Montevideo (Uruguay). Unidad de BioinformáticaWiniarski Erik, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Histología y EmbriologíaMansilla Santiago, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Métodos CuantitativosSimoes Camila, Universidad de la República (Uruguay). Facultad de Medicina. Departamento Básico de MedicinaRodríguez Soledad, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de GenéticaBrandes Mariana, Institut Pasteur de Montevideo (Uruguay). Unidad de BioinformáticaTapié Alejandra, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de GenéticaRodríguez Laura, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de GenéticaCibils Lucía, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de NeuropediatríaAlonso Martina, Universidad de la República (Uruguay). Facultad de Medicina. Centro de Investigaciones Biomédicas (CEINBIO)Martínez Jennyfer, Universidad de la República (Uruguay). Facultad de Medicina. Centro de Investigaciones Biomédicas (CEINBIO)Fernández-Calero Tamara, Universidad Católica del Uruguay (Uruguay). Departamento de Ciencias Exactas y NaturalesDomínguez Fernanda, Universidad Católica del Uruguay (Uruguay)Rosas Mezquida Melania, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de NeuropediatríaCastro Laura, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de BioquímicaCerisola Alfredo, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de NeuropediatríaNaya Hugo, Universidad de la República (Uruguay). Facultad de Agronomía. Departamento de Producción Animal y PasturasCassina Adriana, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de BioquímicaQuijano Celia, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de BioquímicaSpangenberg Lucía, Universidad de la República (Uruguay). Facultad de Medicina. Departamento Básico de Medicina2026-03-13T15:03:50Z2026-03-13T15:03:50Z2023Artículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13 p.application/pdfRaggio V, Graña M, Winiarski E y otros. Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy. Human Genomics [en línea]. 2023;17(1). 13 p.https://hdl.handle.net/20.500.12008/5386110.1186/s40246-023-00463-x1479-7364reponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaenengHuman Genomics. 2023;17(1)Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución (CC - By 4.0)oai:colibri.udelar.edu.uy:20.500.12008/538612026-04-14T10:28:27Z |
| spellingShingle | Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy Raggio, Víctor ATPasas ASOCIADAS CON ACTIVIDADES CELULARES DIVERSAS METABOLISMO ANIMALES BIOPSIA ENCEFALOPATÍAS RATONES MASCULINO MICROCEFALIA MITOCONDRIAS CONVULSIONES GENÉTICA |
| status_str | publishedVersion |
| title | Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy |
| title_full | Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy |
| title_fullStr | Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy |
| title_full_unstemmed | Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy |
| title_short | Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy |
| title_sort | Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy |
| topic | ATPasas ASOCIADAS CON ACTIVIDADES CELULARES DIVERSAS METABOLISMO ANIMALES BIOPSIA ENCEFALOPATÍAS RATONES MASCULINO MICROCEFALIA MITOCONDRIAS CONVULSIONES GENÉTICA |
| url | https://hdl.handle.net/20.500.12008/53861 |