Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy

Abstract 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 heterozyg...
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Autor*in:	Víctor Raggio [verfasserIn] Martín Graña [verfasserIn] Erik Winiarski [verfasserIn] Santiago Mansilla [verfasserIn] Camila Simoes [verfasserIn] Soledad Rodríguez [verfasserIn] Mariana Brandes [verfasserIn] Alejandra Tapié [verfasserIn] Laura Rodríguez [verfasserIn] Lucía Cibils [verfasserIn] Martina Alonso [verfasserIn] Jennyfer Martínez [verfasserIn] Tamara Fernández-Calero [verfasserIn] Fernanda Domínguez [verfasserIn] Melania Rosas Mezquida [verfasserIn] Laura Castro [verfasserIn] Alfredo Cerisola [verfasserIn] Hugo Naya [verfasserIn] Adriana Cassina [verfasserIn] Celia Quijano [verfasserIn] Lucía Spangenberg [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Übergeordnetes Werk:	In: Human Genomics - BMC, 2012, 17(2023), 1, Seite 13
Übergeordnetes Werk:	volume:17 ; year:2023 ; number:1 ; pages:13

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s40246-023-00463-x

Katalog-ID:	DOAJ087721198

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allfields	10.1186/s40246-023-00463-x doi (DE-627)DOAJ087721198 (DE-599)DOAJf35c45e2195e44afad8c9bf9a1ead789 DE-627 ger DE-627 rakwb eng QH426-470 Víctor Raggio verfasserin aut Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Medicine R Genetics Martín Graña verfasserin aut Erik Winiarski verfasserin aut Santiago Mansilla verfasserin aut Camila Simoes verfasserin aut Soledad Rodríguez verfasserin aut Mariana Brandes verfasserin aut Alejandra Tapié verfasserin aut Laura Rodríguez verfasserin aut Lucía Cibils verfasserin aut Martina Alonso verfasserin aut Jennyfer Martínez verfasserin aut Tamara Fernández-Calero verfasserin aut Fernanda Domínguez verfasserin aut Melania Rosas Mezquida verfasserin aut Laura Castro verfasserin aut Alfredo Cerisola verfasserin aut Hugo Naya verfasserin aut Adriana Cassina verfasserin aut Celia Quijano verfasserin aut Lucía Spangenberg verfasserin aut In Human Genomics BMC, 2012 17(2023), 1, Seite 13 (DE-627)388549408 (DE-600)2147618-4 14797364 nnns volume:17 year:2023 number:1 pages:13 https://doi.org/10.1186/s40246-023-00463-x kostenfrei https://doaj.org/article/f35c45e2195e44afad8c9bf9a1ead789 kostenfrei https://doi.org/10.1186/s40246-023-00463-x kostenfrei https://doaj.org/toc/1479-7364 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2023 1 13
spelling	10.1186/s40246-023-00463-x doi (DE-627)DOAJ087721198 (DE-599)DOAJf35c45e2195e44afad8c9bf9a1ead789 DE-627 ger DE-627 rakwb eng QH426-470 Víctor Raggio verfasserin aut Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Medicine R Genetics Martín Graña verfasserin aut Erik Winiarski verfasserin aut Santiago Mansilla verfasserin aut Camila Simoes verfasserin aut Soledad Rodríguez verfasserin aut Mariana Brandes verfasserin aut Alejandra Tapié verfasserin aut Laura Rodríguez verfasserin aut Lucía Cibils verfasserin aut Martina Alonso verfasserin aut Jennyfer Martínez verfasserin aut Tamara Fernández-Calero verfasserin aut Fernanda Domínguez verfasserin aut Melania Rosas Mezquida verfasserin aut Laura Castro verfasserin aut Alfredo Cerisola verfasserin aut Hugo Naya verfasserin aut Adriana Cassina verfasserin aut Celia Quijano verfasserin aut Lucía Spangenberg verfasserin aut In Human Genomics BMC, 2012 17(2023), 1, Seite 13 (DE-627)388549408 (DE-600)2147618-4 14797364 nnns volume:17 year:2023 number:1 pages:13 https://doi.org/10.1186/s40246-023-00463-x kostenfrei https://doaj.org/article/f35c45e2195e44afad8c9bf9a1ead789 kostenfrei https://doi.org/10.1186/s40246-023-00463-x kostenfrei https://doaj.org/toc/1479-7364 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2023 1 13
allfields_unstemmed	10.1186/s40246-023-00463-x doi (DE-627)DOAJ087721198 (DE-599)DOAJf35c45e2195e44afad8c9bf9a1ead789 DE-627 ger DE-627 rakwb eng QH426-470 Víctor Raggio verfasserin aut Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Medicine R Genetics Martín Graña verfasserin aut Erik Winiarski verfasserin aut Santiago Mansilla verfasserin aut Camila Simoes verfasserin aut Soledad Rodríguez verfasserin aut Mariana Brandes verfasserin aut Alejandra Tapié verfasserin aut Laura Rodríguez verfasserin aut Lucía Cibils verfasserin aut Martina Alonso verfasserin aut Jennyfer Martínez verfasserin aut Tamara Fernández-Calero verfasserin aut Fernanda Domínguez verfasserin aut Melania Rosas Mezquida verfasserin aut Laura Castro verfasserin aut Alfredo Cerisola verfasserin aut Hugo Naya verfasserin aut Adriana Cassina verfasserin aut Celia Quijano verfasserin aut Lucía Spangenberg verfasserin aut In Human Genomics BMC, 2012 17(2023), 1, Seite 13 (DE-627)388549408 (DE-600)2147618-4 14797364 nnns volume:17 year:2023 number:1 pages:13 https://doi.org/10.1186/s40246-023-00463-x kostenfrei https://doaj.org/article/f35c45e2195e44afad8c9bf9a1ead789 kostenfrei https://doi.org/10.1186/s40246-023-00463-x kostenfrei https://doaj.org/toc/1479-7364 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2023 1 13
allfieldsGer	10.1186/s40246-023-00463-x doi (DE-627)DOAJ087721198 (DE-599)DOAJf35c45e2195e44afad8c9bf9a1ead789 DE-627 ger DE-627 rakwb eng QH426-470 Víctor Raggio verfasserin aut Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Medicine R Genetics Martín Graña verfasserin aut Erik Winiarski verfasserin aut Santiago Mansilla verfasserin aut Camila Simoes verfasserin aut Soledad Rodríguez verfasserin aut Mariana Brandes verfasserin aut Alejandra Tapié verfasserin aut Laura Rodríguez verfasserin aut Lucía Cibils verfasserin aut Martina Alonso verfasserin aut Jennyfer Martínez verfasserin aut Tamara Fernández-Calero verfasserin aut Fernanda Domínguez verfasserin aut Melania Rosas Mezquida verfasserin aut Laura Castro verfasserin aut Alfredo Cerisola verfasserin aut Hugo Naya verfasserin aut Adriana Cassina verfasserin aut Celia Quijano verfasserin aut Lucía Spangenberg verfasserin aut In Human Genomics BMC, 2012 17(2023), 1, Seite 13 (DE-627)388549408 (DE-600)2147618-4 14797364 nnns volume:17 year:2023 number:1 pages:13 https://doi.org/10.1186/s40246-023-00463-x kostenfrei https://doaj.org/article/f35c45e2195e44afad8c9bf9a1ead789 kostenfrei https://doi.org/10.1186/s40246-023-00463-x kostenfrei https://doaj.org/toc/1479-7364 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2023 1 13
allfieldsSound	10.1186/s40246-023-00463-x doi (DE-627)DOAJ087721198 (DE-599)DOAJf35c45e2195e44afad8c9bf9a1ead789 DE-627 ger DE-627 rakwb eng QH426-470 Víctor Raggio verfasserin aut Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Medicine R Genetics Martín Graña verfasserin aut Erik Winiarski verfasserin aut Santiago Mansilla verfasserin aut Camila Simoes verfasserin aut Soledad Rodríguez verfasserin aut Mariana Brandes verfasserin aut Alejandra Tapié verfasserin aut Laura Rodríguez verfasserin aut Lucía Cibils verfasserin aut Martina Alonso verfasserin aut Jennyfer Martínez verfasserin aut Tamara Fernández-Calero verfasserin aut Fernanda Domínguez verfasserin aut Melania Rosas Mezquida verfasserin aut Laura Castro verfasserin aut Alfredo Cerisola verfasserin aut Hugo Naya verfasserin aut Adriana Cassina verfasserin aut Celia Quijano verfasserin aut Lucía Spangenberg verfasserin aut In Human Genomics BMC, 2012 17(2023), 1, Seite 13 (DE-627)388549408 (DE-600)2147618-4 14797364 nnns volume:17 year:2023 number:1 pages:13 https://doi.org/10.1186/s40246-023-00463-x kostenfrei https://doaj.org/article/f35c45e2195e44afad8c9bf9a1ead789 kostenfrei https://doi.org/10.1186/s40246-023-00463-x kostenfrei https://doaj.org/toc/1479-7364 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 17 2023 1 13
language	English
source	In Human Genomics 17(2023), 1, Seite 13 volume:17 year:2023 number:1 pages:13
sourceStr	In Human Genomics 17(2023), 1, Seite 13 volume:17 year:2023 number:1 pages:13
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Medicine R Genetics
isfreeaccess_bool	true
container_title	Human Genomics
authorswithroles_txt_mv	Víctor Raggio @@aut@@ Martín Graña @@aut@@ Erik Winiarski @@aut@@ Santiago Mansilla @@aut@@ Camila Simoes @@aut@@ Soledad Rodríguez @@aut@@ Mariana Brandes @@aut@@ Alejandra Tapié @@aut@@ Laura Rodríguez @@aut@@ Lucía Cibils @@aut@@ Martina Alonso @@aut@@ Jennyfer Martínez @@aut@@ Tamara Fernández-Calero @@aut@@ Fernanda Domínguez @@aut@@ Melania Rosas Mezquida @@aut@@ Laura Castro @@aut@@ Alfredo Cerisola @@aut@@ Hugo Naya @@aut@@ Adriana Cassina @@aut@@ Celia Quijano @@aut@@ Lucía Spangenberg @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	388549408
id	DOAJ087721198
language_de	englisch
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callnumber-first	Q - Science
author	Víctor Raggio
spellingShingle	Víctor Raggio misc QH426-470 misc Medicine misc R misc Genetics Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy
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topic_title	QH426-470 Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy
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title	Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy
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title_full	Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy
author_sort	Víctor Raggio
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author_browse	Víctor Raggio Martín Graña Erik Winiarski Santiago Mansilla Camila Simoes Soledad Rodríguez Mariana Brandes Alejandra Tapié Laura Rodríguez Lucía Cibils Martina Alonso Jennyfer Martínez Tamara Fernández-Calero Fernanda Domínguez Melania Rosas Mezquida Laura Castro Alfredo Cerisola Hugo Naya Adriana Cassina Celia Quijano Lucía Spangenberg
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title_sort	computational and mitochondrial functional studies of novel compound heterozygous variants in spata5 gene support a causal link with epileptogenic encephalopathy
callnumber	QH426-470
title_auth	Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy
abstract	Abstract 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.
abstractGer	Abstract 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.
abstract_unstemmed	Abstract 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.
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title_short	Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy
url	https://doi.org/10.1186/s40246-023-00463-x https://doaj.org/article/f35c45e2195e44afad8c9bf9a1ead789 https://doaj.org/toc/1479-7364
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up_date	2024-07-03T13:31:47.134Z
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Computational and mitochondrial functional studies of novel compound heterozygous variants in SPATA5 gene support a causal link with epileptogenic encephalopathy

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