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; Henry Houlden

doi:10.1038/s41467-024-46354-0

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

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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, …

Nature Communications, Vol.15(1)

2024

DOI: https://doi.org/10.1038/s41467-024-46354-0

Résumé

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.

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Titre: Biallelic NAA60 variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications
Créateurs - sans rôle: Viorica Chelban - University College London
Henriette Aksnes - University of Bergen
Reza Maroofian - University College London
Lauren C Lamonica - Yale University
Luis Seabra - Université Paris Cité
Anette Siggervåg - University of Bergen
Perrine Devic - Hospices Civils de Lyon
Hanan E Shamseldin - King Faisal Specialist Hospital & Research Centre
Jana Vandrovcova - University College London
David Murphy - National Hospital for Neurology and Neurosurgery
Anne-Claire Richard - Génomique du cancer et du cerveau
Olivier Quenez - Inserm
Antoine Bonnevalle - Université de Rouen Normandie
M. Natalia Zanetti - University College London
Rauan Kaiyrzhanov - National Hospital for Neurology and Neurosurgery
Vincenzo Salpietro - University College London
Stephanie Efthymiou - National Hospital for Neurology and Neurosurgery
Lucia V Schottlaender - University College London
Heba Morsy - University College London
Annarita Scardamaglia - National Hospital for Neurology and Neurosurgery
Ambreen Tariq
Alistair T Pagnamenta - 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 - Centre National de la Recherche Scientifique
Andrés Moreno de Luca
Anne Boland-Auge
Robert Olaso - Centre National de Recherche en Génomique Humaine
Jean-François Deleuze - Centre National de Recherche en Génomique Humaine
Mathieu Anheim - Université de Strasbourg
Benjamin Cretin - Université de Strasbourg
Barbara Vona - Universitätsmedizin Göttingen
Fahad Alajlan
Firdous Abdulwahab - King Faisal Specialist Hospital & Research Centre
Jean-Luc Battini - Université de Montpellier, Institut de Recherche en Infectiologie de Montpellier - IRIM
Rojan İpek - Dicle University
Peter Bauer - Centogene
Giovanni Zifarelli - Centogene
Serdal Gungor - Inonu University
Semra Hiz Kurul - Dokuz Eylül University
Hanns Lochmuller - Ottawa Hospital
Sahar I Da’as - Hamad bin Khalifa University
Khalid A Fakhro - Weill Cornell Medical College in Qatar
Alicia Gómez-Pascual - Universidad de Murcia
Juan A Botía - Universidad de Murcia
Nicholas W Wood - University College London
Rita Horvath - University of Cambridge
Andreas M Ernst - Yale University
James E Rothman - Yale University
Meriel Mcentagart - St George’s University Hospitals NHS Foundation Trust
Yanick J Crow - University of Edinburgh
Fowzan S Alkuraya - King Faisal Specialist Hospital & Research Centre
Fowzan S Alkuraya - King Faisal Specialist Hospital & Research Centre
Gaël Nicolas - Université de Rouen Normandie
Thomas Arnesen - Haukeland University Hospital
Henry Houlden - University College London
Détails de publication: Nature Communications, Vol.15(1)
Identifiants: 99150547209311
Unité académique: Institut de Recherche en Infectiologie de Montpellier - IRIM
Langue: English
Type de ressource: Journal article
Champs locaux: hal-04905283