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

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

<p dir="ltr">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...

Full description

Saved in:
Bibliographic Details
Main Author: Viorica Chelban (4569337) (author)
Other Authors: Henriette Aksnes (205652) (author), Reza Maroofian (5237852) (author), Lauren C. LaMonica (19342717) (author), Luis Seabra (19342720) (author), Anette Siggervåg (19342723) (author), Perrine Devic (17843042) (author), Hanan E. Shamseldin (8987366) (author), Jana Vandrovcova (90909) (author), David Murphy (483511) (author), Anne-Claire Richard (3873238) (author), Olivier Quenez (3282843) (author), Antoine Bonnevalle (19342726) (author), M. Natalia Zanetti (19342729) (author), Rauan Kaiyrzhanov (11494177) (author), Vincenzo Salpietro (4569352) (author), Stephanie Efthymiou (4569349) (author), Lucia V. Schottlaender (19342732) (author), Heba Morsy (3485405) (author), Annarita Scardamaglia (16423404) (author), Ambreen Tariq (19342735) (author), Alistair T. Pagnamenta (6380606) (author), Ajia Pennavaria (19342738) (author), Liv S. Krogstad (19342741) (author), Åse K. Bekkelund (19342744) (author), Alessia Caiella (19342747) (author), Nina Glomnes (205655) (author), Kirsten M. Brønstad (19342750) (author), Sandrine Tury (5812580) (author), Andrés Moreno De Luca (19342753) (author), Anne Boland-Auge (8536302) (author), Robert Olaso (82489) (author), Jean-François Deleuze (3626111) (author), Mathieu Anheim (241061) (author), Benjamin Cretin (303294) (author), Barbara Vona (5237843) (author), Fahad Alajlan (18078073) (author), Firdous Abdulwahab (3485432) (author), Jean-Luc Battini (19342756) (author), Rojan İpek (19342759) (author), Peter Bauer (524851) (author), Giovanni Zifarelli (17487201) (author), Serdal Gungor (13015697) (author), Semra Hiz Kurul (19342762) (author), Hanns Lochmuller (5280071) (author), Sahar I. Da’as (9631717) (author), Khalid A. Fakhro (3158862) (author), Alicia Gómez-Pascual (15250291) (author), Juan A. Botía (7947932) (author), Nicholas W. Wood (49276) (author), Rita Horvath (4474222) (author), Andreas M. Ernst (19342765) (author), James E. Rothman (369943) (author), Meriel McEntagart (2636713) (author), Yanick J. Crow (9433775) (author), Fowzan S. Alkuraya (8791703) (author), Gaël Nicolas (3873235) (author), SYNaPS Study Group (19342768) (author), Henry Houlden (110428) (author), Thomas Arnesen (109198) (author)
Published: 2024
Subjects:
Biological sciences
Genetics
Biomedical and clinical sciences
Neurosciences
Acetylation
Disease genetics
Mechanisms of disease
Movement disorders
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:<p dir="ltr">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 <i>NAA60</i> 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 <i>NAA60</i> in vitro. In cells, loss of <i>NAA60</i> caused reduced surface levels of SLC20A2 and a reduction in extracellular phosphate uptake. This study establishes <i>NAA60</i> as a causal gene for PFBC, provides a possible biochemical explanation of its disease-causing mechanisms and underscores <i>NAA60</i>-mediated Nt-acetylation of transmembrane proteins as a fundamental process for healthy neurobiological functioning.</p><h2>Other Information</h2><p dir="ltr">Published in: Nature Communications<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41467-024-46354-0" target="_blank">https://dx.doi.org/10.1038/s41467-024-46354-0</a></p>

Similar Items