Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications
- Autores
- Chelban, Viorica; Aksnes, Henriette; Maroofian, Reza; LaMonica, Lauren C.; Seabra, Luis; Siggervåg, Anette; Devic, Perrine; Shamseldin, Hanan E.; Vandrovcova, Jana; Murphy, David; Richard, Anne Claire; Quenez, Olivier; Bonnevalle, Antoine; Zanetti, Maria Natalia; Kaiyrzhanov, Rauan; Salpietro, Vincenzo; Efthymiou, Stephanie; Schottlaender, Lucia Valentina; Morsy, Heba; Scardamaglia, Annarita; Tariq, Ambreen; Pagnamenta, Alistair T.; Pennavaria, Ajia; Krogstad, Liv S.; Bekkelund, Åse K.; Crow, Yanick J.; Alkuraya, Fowzan S.; Nicolas, Gaël; Arnesen, Thomas; Houlden, Henry
- Año de publicación
- 2024
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Primary familial brain calcification (PFBC) is characterized by calcium deposition in the brain, causing progressive movement disorders, psychiatric symptoms, and cognitive decline. PFBC is a heterogeneous disorder currently linked to variants in six different genes, but most patients remain genetically undiagnosed. Here, we identify biallelic NAA60 variants in ten individuals from seven families with autosomal recessive PFBC. The NAA60 variants lead to loss-of-function with lack of protein N-terminal (Nt)-acetylation activity. We show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro. In cells, loss of NAA60 caused reduced surface levels of SLC20A2 and a reduction in extracellular phosphate uptake. This study establishes NAA60 as a causal gene for PFBC, provides a possible biochemical explanation of its disease-causing mechanisms and underscores NAA60-mediated Nt-acetylation of transmembrane proteins as a fundamental process for healthy neurobiological functioning.
Fil: Chelban, Viorica. State University of Medicine and Pharmacy; Moldavia. University College London; Reino Unido
Fil: Aksnes, Henriette. University of Bergen; Noruega
Fil: Maroofian, Reza. University College London; Reino Unido
Fil: LaMonica, Lauren C.. University of Yale; Estados Unidos
Fil: Seabra, Luis. Université Paris Cité; Francia
Fil: Siggervåg, Anette. University of Bergen; Noruega
Fil: Devic, Perrine. Hospices Civils de Lyon; Francia
Fil: Shamseldin, Hanan E.. King Faisal Specialist Hospital and Research Center; Arabia Saudita
Fil: Vandrovcova, Jana. University College London; Reino Unido
Fil: Murphy, David. University College London; Reino Unido
Fil: Richard, Anne Claire. Université de Rouen-Normandie ; Francia
Fil: Quenez, Olivier. Université de Rouen-Normandie ; Francia
Fil: Bonnevalle, Antoine. Université de Rouen-Normandie ; Francia
Fil: Zanetti, Maria Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. University College London; Reino Unido
Fil: Kaiyrzhanov, Rauan. University College London; Reino Unido
Fil: Salpietro, Vincenzo. University College London; Reino Unido
Fil: Efthymiou, Stephanie. University College London; Reino Unido
Fil: Schottlaender, Lucia Valentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. University College London; Reino Unido
Fil: Morsy, Heba. University College London; Reino Unido. Alexandria University; Egipto
Fil: Scardamaglia, Annarita. University College London; Reino Unido
Fil: Tariq, Ambreen. University College London; Reino Unido
Fil: Pagnamenta, Alistair T.. University of Oxford. Wellcome Genome Campus. Centre for Genomic Pathogen Surveillance; Reino Unido
Fil: Pennavaria, Ajia. University of Bergen; Noruega
Fil: Krogstad, Liv S.. University of Bergen; Noruega
Fil: Bekkelund, Åse K.. University of Bergen; Noruega
Fil: Crow, Yanick J.. Université Paris Cité; Francia. University of Edinburgh; Reino Unido
Fil: Alkuraya, Fowzan S.. Alfaisal University; Arabia Saudita
Fil: Nicolas, Gaël. Université de Rouen Normandie; Francia
Fil: Arnesen, Thomas. University of Bergen; Noruega. Haukeland University Hospital; Noruega
Fil: Houlden, Henry. University College London Hospitals; Reino Unido - Materia
-
NAA60
Acetylation
Brain calcification
Movement disorders - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/276461
Ver los metadatos del registro completo
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Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcificationsChelban, VioricaAksnes, HenrietteMaroofian, RezaLaMonica, Lauren C.Seabra, LuisSiggervåg, AnetteDevic, PerrineShamseldin, Hanan E.Vandrovcova, JanaMurphy, DavidRichard, Anne ClaireQuenez, OlivierBonnevalle, AntoineZanetti, Maria NataliaKaiyrzhanov, RauanSalpietro, VincenzoEfthymiou, StephanieSchottlaender, Lucia ValentinaMorsy, HebaScardamaglia, AnnaritaTariq, AmbreenPagnamenta, Alistair T.Pennavaria, AjiaKrogstad, Liv S.Bekkelund, Åse K.Crow, Yanick J.Alkuraya, Fowzan S.Nicolas, GaëlArnesen, ThomasHoulden, HenryNAA60AcetylationBrain calcificationMovement disordershttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Primary familial brain calcification (PFBC) is characterized by calcium deposition in the brain, causing progressive movement disorders, psychiatric symptoms, and cognitive decline. PFBC is a heterogeneous disorder currently linked to variants in six different genes, but most patients remain genetically undiagnosed. Here, we identify biallelic NAA60 variants in ten individuals from seven families with autosomal recessive PFBC. The NAA60 variants lead to loss-of-function with lack of protein N-terminal (Nt)-acetylation activity. We show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro. In cells, loss of NAA60 caused reduced surface levels of SLC20A2 and a reduction in extracellular phosphate uptake. This study establishes NAA60 as a causal gene for PFBC, provides a possible biochemical explanation of its disease-causing mechanisms and underscores NAA60-mediated Nt-acetylation of transmembrane proteins as a fundamental process for healthy neurobiological functioning.Fil: Chelban, Viorica. State University of Medicine and Pharmacy; Moldavia. University College London; Reino UnidoFil: Aksnes, Henriette. University of Bergen; NoruegaFil: Maroofian, Reza. University College London; Reino UnidoFil: LaMonica, Lauren C.. University of Yale; Estados UnidosFil: Seabra, Luis. Université Paris Cité; FranciaFil: Siggervåg, Anette. University of Bergen; NoruegaFil: Devic, Perrine. Hospices Civils de Lyon; FranciaFil: Shamseldin, Hanan E.. King Faisal Specialist Hospital and Research Center; Arabia SauditaFil: Vandrovcova, Jana. University College London; Reino UnidoFil: Murphy, David. University College London; Reino UnidoFil: Richard, Anne Claire. Université de Rouen-Normandie ; FranciaFil: Quenez, Olivier. Université de Rouen-Normandie ; FranciaFil: Bonnevalle, Antoine. Université de Rouen-Normandie ; FranciaFil: Zanetti, Maria Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. University College London; Reino UnidoFil: Kaiyrzhanov, Rauan. University College London; Reino UnidoFil: Salpietro, Vincenzo. University College London; Reino UnidoFil: Efthymiou, Stephanie. University College London; Reino UnidoFil: Schottlaender, Lucia Valentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. University College London; Reino UnidoFil: Morsy, Heba. University College London; Reino Unido. Alexandria University; EgiptoFil: Scardamaglia, Annarita. University College London; Reino UnidoFil: Tariq, Ambreen. University College London; Reino UnidoFil: Pagnamenta, Alistair T.. University of Oxford. Wellcome Genome Campus. Centre for Genomic Pathogen Surveillance; Reino UnidoFil: Pennavaria, Ajia. University of Bergen; NoruegaFil: Krogstad, Liv S.. University of Bergen; NoruegaFil: Bekkelund, Åse K.. University of Bergen; NoruegaFil: Crow, Yanick J.. Université Paris Cité; Francia. University of Edinburgh; Reino UnidoFil: Alkuraya, Fowzan S.. Alfaisal University; Arabia SauditaFil: Nicolas, Gaël. Université de Rouen Normandie; FranciaFil: Arnesen, Thomas. University of Bergen; Noruega. Haukeland University Hospital; NoruegaFil: Houlden, Henry. University College London Hospitals; Reino UnidoNature2024-03-13info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/276461Chelban, Viorica; Aksnes, Henriette; Maroofian, Reza; LaMonica, Lauren C.; Seabra, Luis; et al.; Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications; Nature; Nature Communications; 15; 1; 13-3-2024; 1-202041-1723CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41467-024-46354-0info:eu-repo/semantics/altIdentifier/doi/10.1038/s41467-024-46354-0info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-23T13:33:15Zoai:ri.conicet.gov.ar:11336/276461instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-12-23 13:33:15.654CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications |
| title |
Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications |
| spellingShingle |
Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications Chelban, Viorica NAA60 Acetylation Brain calcification Movement disorders |
| title_short |
Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications |
| title_full |
Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications |
| title_fullStr |
Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications |
| title_full_unstemmed |
Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications |
| title_sort |
Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications |
| dc.creator.none.fl_str_mv |
Chelban, Viorica Aksnes, Henriette Maroofian, Reza LaMonica, Lauren C. Seabra, Luis Siggervåg, Anette Devic, Perrine Shamseldin, Hanan E. Vandrovcova, Jana Murphy, David Richard, Anne Claire Quenez, Olivier Bonnevalle, Antoine Zanetti, Maria Natalia Kaiyrzhanov, Rauan Salpietro, Vincenzo Efthymiou, Stephanie Schottlaender, Lucia Valentina Morsy, Heba Scardamaglia, Annarita Tariq, Ambreen Pagnamenta, Alistair T. Pennavaria, Ajia Krogstad, Liv S. Bekkelund, Åse K. Crow, Yanick J. Alkuraya, Fowzan S. Nicolas, Gaël Arnesen, Thomas Houlden, Henry |
| author |
Chelban, Viorica |
| author_facet |
Chelban, Viorica Aksnes, Henriette Maroofian, Reza LaMonica, Lauren C. Seabra, Luis Siggervåg, Anette Devic, Perrine Shamseldin, Hanan E. Vandrovcova, Jana Murphy, David Richard, Anne Claire Quenez, Olivier Bonnevalle, Antoine Zanetti, Maria Natalia Kaiyrzhanov, Rauan Salpietro, Vincenzo Efthymiou, Stephanie Schottlaender, Lucia Valentina Morsy, Heba Scardamaglia, Annarita Tariq, Ambreen Pagnamenta, Alistair T. Pennavaria, Ajia Krogstad, Liv S. Bekkelund, Åse K. Crow, Yanick J. Alkuraya, Fowzan S. Nicolas, Gaël Arnesen, Thomas Houlden, Henry |
| author_role |
author |
| author2 |
Aksnes, Henriette Maroofian, Reza LaMonica, Lauren C. Seabra, Luis Siggervåg, Anette Devic, Perrine Shamseldin, Hanan E. Vandrovcova, Jana Murphy, David Richard, Anne Claire Quenez, Olivier Bonnevalle, Antoine Zanetti, Maria Natalia Kaiyrzhanov, Rauan Salpietro, Vincenzo Efthymiou, Stephanie Schottlaender, Lucia Valentina Morsy, Heba Scardamaglia, Annarita Tariq, Ambreen Pagnamenta, Alistair T. Pennavaria, Ajia Krogstad, Liv S. Bekkelund, Åse K. Crow, Yanick J. Alkuraya, Fowzan S. Nicolas, Gaël Arnesen, Thomas Houlden, Henry |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
NAA60 Acetylation Brain calcification Movement disorders |
| topic |
NAA60 Acetylation Brain calcification Movement disorders |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| dc.description.none.fl_txt_mv |
Primary familial brain calcification (PFBC) is characterized by calcium deposition in the brain, causing progressive movement disorders, psychiatric symptoms, and cognitive decline. PFBC is a heterogeneous disorder currently linked to variants in six different genes, but most patients remain genetically undiagnosed. Here, we identify biallelic NAA60 variants in ten individuals from seven families with autosomal recessive PFBC. The NAA60 variants lead to loss-of-function with lack of protein N-terminal (Nt)-acetylation activity. We show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro. In cells, loss of NAA60 caused reduced surface levels of SLC20A2 and a reduction in extracellular phosphate uptake. This study establishes NAA60 as a causal gene for PFBC, provides a possible biochemical explanation of its disease-causing mechanisms and underscores NAA60-mediated Nt-acetylation of transmembrane proteins as a fundamental process for healthy neurobiological functioning. Fil: Chelban, Viorica. State University of Medicine and Pharmacy; Moldavia. University College London; Reino Unido Fil: Aksnes, Henriette. University of Bergen; Noruega Fil: Maroofian, Reza. University College London; Reino Unido Fil: LaMonica, Lauren C.. University of Yale; Estados Unidos Fil: Seabra, Luis. Université Paris Cité; Francia Fil: Siggervåg, Anette. University of Bergen; Noruega Fil: Devic, Perrine. Hospices Civils de Lyon; Francia Fil: Shamseldin, Hanan E.. King Faisal Specialist Hospital and Research Center; Arabia Saudita Fil: Vandrovcova, Jana. University College London; Reino Unido Fil: Murphy, David. University College London; Reino Unido Fil: Richard, Anne Claire. Université de Rouen-Normandie ; Francia Fil: Quenez, Olivier. Université de Rouen-Normandie ; Francia Fil: Bonnevalle, Antoine. Université de Rouen-Normandie ; Francia Fil: Zanetti, Maria Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. University College London; Reino Unido Fil: Kaiyrzhanov, Rauan. University College London; Reino Unido Fil: Salpietro, Vincenzo. University College London; Reino Unido Fil: Efthymiou, Stephanie. University College London; Reino Unido Fil: Schottlaender, Lucia Valentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. University College London; Reino Unido Fil: Morsy, Heba. University College London; Reino Unido. Alexandria University; Egipto Fil: Scardamaglia, Annarita. University College London; Reino Unido Fil: Tariq, Ambreen. University College London; Reino Unido Fil: Pagnamenta, Alistair T.. University of Oxford. Wellcome Genome Campus. Centre for Genomic Pathogen Surveillance; Reino Unido Fil: Pennavaria, Ajia. University of Bergen; Noruega Fil: Krogstad, Liv S.. University of Bergen; Noruega Fil: Bekkelund, Åse K.. University of Bergen; Noruega Fil: Crow, Yanick J.. Université Paris Cité; Francia. University of Edinburgh; Reino Unido Fil: Alkuraya, Fowzan S.. Alfaisal University; Arabia Saudita Fil: Nicolas, Gaël. Université de Rouen Normandie; Francia Fil: Arnesen, Thomas. University of Bergen; Noruega. Haukeland University Hospital; Noruega Fil: Houlden, Henry. University College London Hospitals; Reino Unido |
| description |
Primary familial brain calcification (PFBC) is characterized by calcium deposition in the brain, causing progressive movement disorders, psychiatric symptoms, and cognitive decline. PFBC is a heterogeneous disorder currently linked to variants in six different genes, but most patients remain genetically undiagnosed. Here, we identify biallelic NAA60 variants in ten individuals from seven families with autosomal recessive PFBC. The NAA60 variants lead to loss-of-function with lack of protein N-terminal (Nt)-acetylation activity. We show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro. In cells, loss of NAA60 caused reduced surface levels of SLC20A2 and a reduction in extracellular phosphate uptake. This study establishes NAA60 as a causal gene for PFBC, provides a possible biochemical explanation of its disease-causing mechanisms and underscores NAA60-mediated Nt-acetylation of transmembrane proteins as a fundamental process for healthy neurobiological functioning. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024-03-13 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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publishedVersion |
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http://hdl.handle.net/11336/276461 Chelban, Viorica; Aksnes, Henriette; Maroofian, Reza; LaMonica, Lauren C.; Seabra, Luis; et al.; Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications; Nature; Nature Communications; 15; 1; 13-3-2024; 1-20 2041-1723 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/276461 |
| identifier_str_mv |
Chelban, Viorica; Aksnes, Henriette; Maroofian, Reza; LaMonica, Lauren C.; Seabra, Luis; et al.; Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications; Nature; Nature Communications; 15; 1; 13-3-2024; 1-20 2041-1723 CONICET Digital CONICET |
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eng |
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eng |
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