Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications

Viorica Chelban (), Henriette Aksnes (), Reza Maroofian, Lauren C. LaMonica, Luis Seabra, Anette Siggervåg, Perrine Devic, Hanan E. Shamseldin, Jana Vandrovcova, David Murphy, Anne-Claire Richard, Olivier Quenez, Antoine Bonnevalle, M. Natalia Zanetti, Rauan Kaiyrzhanov, Vincenzo Salpietro, Stephanie Efthymiou, Lucia V. Schottlaender, Heba Morsy, Annarita Scardamaglia, Ambreen Tariq, Alistair T. Pagnamenta, Ajia Pennavaria, Liv S. Krogstad, Åse K. Bekkelund, Alessia Caiella, Nina Glomnes, Kirsten M. Brønstad, Sandrine Tury, Andrés Moreno De Luca, Anne Boland-Auge, Robert Olaso, Jean-François Deleuze, Mathieu Anheim, Benjamin Cretin, Barbara Vona, Fahad Alajlan, Firdous Abdulwahab, Jean-Luc Battini, Rojan İpek, Peter Bauer, Giovanni Zifarelli, Serdal Gungor, Semra Hiz Kurul, Hanns Lochmuller, Sahar I. Da’as, Khalid A. Fakhro, Alicia Gómez-Pascual, Juan A. Botía, Nicholas W. Wood, Rita Horvath, Andreas M. Ernst, James E. Rothman, Meriel McEntagart, Yanick J. Crow, Fowzan S. Alkuraya, Gaël Nicolas, Thomas Arnesen () and Henry Houlden ()
Additional contact information
Viorica Chelban: UCL Queen Square Institute of Neurology
Henriette Aksnes: University of Bergen
Reza Maroofian: UCL Queen Square Institute of Neurology
Lauren C. LaMonica: Yale School of Medicine
Luis Seabra: INSERM UMR 1163
Anette Siggervåg: University of Bergen
Perrine Devic: Service d’Explorations Fonctionnelles Neurologiques
Hanan E. Shamseldin: King Faisal Specialist Hospital and Research Center
Jana Vandrovcova: UCL Queen Square Institute of Neurology
David Murphy: UCL Queen Square Institute of Neurology
Anne-Claire Richard: Department of Genetics and CNRMAJ
Olivier Quenez: Department of Genetics and CNRMAJ
Antoine Bonnevalle: Department of Genetics and CNRMAJ
M. Natalia Zanetti: UCL Queen Square Institute of Neurology
Rauan Kaiyrzhanov: UCL Queen Square Institute of Neurology
Vincenzo Salpietro: UCL Queen Square Institute of Neurology
Stephanie Efthymiou: UCL Queen Square Institute of Neurology
Lucia V. Schottlaender: UCL Queen Square Institute of Neurology
Heba Morsy: UCL Queen Square Institute of Neurology
Annarita Scardamaglia: UCL Queen Square Institute of Neurology
Ambreen Tariq: UCL Queen Square Institute of Neurology
Alistair T. Pagnamenta: Wellcome Centre for Human Genetics
Ajia Pennavaria: University of Bergen
Liv S. Krogstad: University of Bergen
Åse K. Bekkelund: University of Bergen
Alessia Caiella: University of Bergen
Nina Glomnes: University of Bergen
Kirsten M. Brønstad: University of Bergen
Sandrine Tury: Université de Montpellier, CNRS
Andrés Moreno De Luca: Autism & Developmental Medicine Institute, Geisinger
Anne Boland-Auge: Centre National de Recherche en Génomique Humaine (CNRGH)
Robert Olaso: Centre National de Recherche en Génomique Humaine (CNRGH)
Jean-François Deleuze: Centre National de Recherche en Génomique Humaine (CNRGH)
Mathieu Anheim: Strasbourg University Hospital
Benjamin Cretin: Strasbourg University Hospital
Barbara Vona: University Medical Center Göttingen
Fahad Alajlan: King Faisal Specialist Hospital and Research Center
Firdous Abdulwahab: King Faisal Specialist Hospital and Research Center
Jean-Luc Battini: Université de Montpellier, CNRS
Rojan İpek: Dicle University
Peter Bauer: Centogene GmbH
Giovanni Zifarelli: Centogene GmbH
Serdal Gungor: Division of Pediatric Neurology
Semra Hiz Kurul: Department of Paediatric Neurology
Hanns Lochmuller: The Ottawa Hospital
Sahar I. Da’as: Sidra Medicine
Khalid A. Fakhro: Sidra Medicine
Alicia Gómez-Pascual: University of Murcia, Campus Espinardo
Juan A. Botía: University of Murcia, Campus Espinardo
Nicholas W. Wood: UCL Queen Square Institute of Neurology
Rita Horvath: University of Cambridge
Andreas M. Ernst: Yale School of Medicine
James E. Rothman: Yale School of Medicine
Meriel McEntagart: St George’s University Hospitals
Yanick J. Crow: INSERM UMR 1163
Fowzan S. Alkuraya: King Faisal Specialist Hospital and Research Center
Gaël Nicolas: Department of Genetics and CNRMAJ
Thomas Arnesen: University of Bergen
Henry Houlden: UCL Queen Square Institute of Neurology

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-024-46354-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46354-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-46354-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().