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

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...

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المؤلف الرئيسي:	Viorica Chelban (4569337) (author)
مؤلفون آخرون:	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)
منشور في:	2024
الموضوعات:	Biological sciences Genetics Biomedical and clinical sciences Neurosciences Acetylation Disease genetics Mechanisms of disease Movement disorders
الوسوم:	إضافة وسم لا توجد وسوم, كن أول من يضع وسما على هذه التسجيلة!

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author	Viorica Chelban (4569337)
author2	Henriette Aksnes (205652) Reza Maroofian (5237852) Lauren C. LaMonica (19342717) Luis Seabra (19342720) Anette Siggervåg (19342723) Perrine Devic (17843042) Hanan E. Shamseldin (8987366) Jana Vandrovcova (90909) David Murphy (483511) Anne-Claire Richard (3873238) Olivier Quenez (3282843) Antoine Bonnevalle (19342726) M. Natalia Zanetti (19342729) Rauan Kaiyrzhanov (11494177) Vincenzo Salpietro (4569352) Stephanie Efthymiou (4569349) Lucia V. Schottlaender (19342732) Heba Morsy (3485405) Annarita Scardamaglia (16423404) Ambreen Tariq (19342735) Alistair T. Pagnamenta (6380606) Ajia Pennavaria (19342738) Liv S. Krogstad (19342741) Åse K. Bekkelund (19342744) Alessia Caiella (19342747) Nina Glomnes (205655) Kirsten M. Brønstad (19342750) Sandrine Tury (5812580) Andrés Moreno De Luca (19342753) Anne Boland-Auge (8536302) Robert Olaso (82489) Jean-François Deleuze (3626111) Mathieu Anheim (241061) Benjamin Cretin (303294) Barbara Vona (5237843) Fahad Alajlan (18078073) Firdous Abdulwahab (3485432) Jean-Luc Battini (19342756) Rojan İpek (19342759) Peter Bauer (524851) Giovanni Zifarelli (17487201) Serdal Gungor (13015697) Semra Hiz Kurul (19342762) Hanns Lochmuller (5280071) Sahar I. Da’as (9631717) Khalid A. Fakhro (3158862) Alicia Gómez-Pascual (15250291) Juan A. Botía (7947932) Nicholas W. Wood (49276) Rita Horvath (4474222) Andreas M. Ernst (19342765) James E. Rothman (369943) Meriel McEntagart (2636713) Yanick J. Crow (9433775) Fowzan S. Alkuraya (8791703) Gaël Nicolas (3873235) SYNaPS Study Group (19342768) Henry Houlden (110428) Thomas Arnesen (109198)
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 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 author
author_facet	Viorica Chelban (4569337) Henriette Aksnes (205652) Reza Maroofian (5237852) Lauren C. LaMonica (19342717) Luis Seabra (19342720) Anette Siggervåg (19342723) Perrine Devic (17843042) Hanan E. Shamseldin (8987366) Jana Vandrovcova (90909) David Murphy (483511) Anne-Claire Richard (3873238) Olivier Quenez (3282843) Antoine Bonnevalle (19342726) M. Natalia Zanetti (19342729) Rauan Kaiyrzhanov (11494177) Vincenzo Salpietro (4569352) Stephanie Efthymiou (4569349) Lucia V. Schottlaender (19342732) Heba Morsy (3485405) Annarita Scardamaglia (16423404) Ambreen Tariq (19342735) Alistair T. Pagnamenta (6380606) Ajia Pennavaria (19342738) Liv S. Krogstad (19342741) Åse K. Bekkelund (19342744) Alessia Caiella (19342747) Nina Glomnes (205655) Kirsten M. Brønstad (19342750) Sandrine Tury (5812580) Andrés Moreno De Luca (19342753) Anne Boland-Auge (8536302) Robert Olaso (82489) Jean-François Deleuze (3626111) Mathieu Anheim (241061) Benjamin Cretin (303294) Barbara Vona (5237843) Fahad Alajlan (18078073) Firdous Abdulwahab (3485432) Jean-Luc Battini (19342756) Rojan İpek (19342759) Peter Bauer (524851) Giovanni Zifarelli (17487201) Serdal Gungor (13015697) Semra Hiz Kurul (19342762) Hanns Lochmuller (5280071) Sahar I. Da’as (9631717) Khalid A. Fakhro (3158862) Alicia Gómez-Pascual (15250291) Juan A. Botía (7947932) Nicholas W. Wood (49276) Rita Horvath (4474222) Andreas M. Ernst (19342765) James E. Rothman (369943) Meriel McEntagart (2636713) Yanick J. Crow (9433775) Fowzan S. Alkuraya (8791703) Gaël Nicolas (3873235) SYNaPS Study Group (19342768) Henry Houlden (110428) Thomas Arnesen (109198)
author_role	author
dc.creator.none.fl_str_mv	Viorica Chelban (4569337) Henriette Aksnes (205652) Reza Maroofian (5237852) Lauren C. LaMonica (19342717) Luis Seabra (19342720) Anette Siggervåg (19342723) Perrine Devic (17843042) Hanan E. Shamseldin (8987366) Jana Vandrovcova (90909) David Murphy (483511) Anne-Claire Richard (3873238) Olivier Quenez (3282843) Antoine Bonnevalle (19342726) M. Natalia Zanetti (19342729) Rauan Kaiyrzhanov (11494177) Vincenzo Salpietro (4569352) Stephanie Efthymiou (4569349) Lucia V. Schottlaender (19342732) Heba Morsy (3485405) Annarita Scardamaglia (16423404) Ambreen Tariq (19342735) Alistair T. Pagnamenta (6380606) Ajia Pennavaria (19342738) Liv S. Krogstad (19342741) Åse K. Bekkelund (19342744) Alessia Caiella (19342747) Nina Glomnes (205655) Kirsten M. Brønstad (19342750) Sandrine Tury (5812580) Andrés Moreno De Luca (19342753) Anne Boland-Auge (8536302) Robert Olaso (82489) Jean-François Deleuze (3626111) Mathieu Anheim (241061) Benjamin Cretin (303294) Barbara Vona (5237843) Fahad Alajlan (18078073) Firdous Abdulwahab (3485432) Jean-Luc Battini (19342756) Rojan İpek (19342759) Peter Bauer (524851) Giovanni Zifarelli (17487201) Serdal Gungor (13015697) Semra Hiz Kurul (19342762) Hanns Lochmuller (5280071) Sahar I. Da’as (9631717) Khalid A. Fakhro (3158862) Alicia Gómez-Pascual (15250291) Juan A. Botía (7947932) Nicholas W. Wood (49276) Rita Horvath (4474222) Andreas M. Ernst (19342765) James E. Rothman (369943) Meriel McEntagart (2636713) Yanick J. Crow (9433775) Fowzan S. Alkuraya (8791703) Gaël Nicolas (3873235) SYNaPS Study Group (19342768) Henry Houlden (110428) Thomas Arnesen (109198)
dc.date.none.fl_str_mv	2024-03-13T09:00:00Z
dc.identifier.none.fl_str_mv	10.1038/s41467-024-46354-0
dc.relation.none.fl_str_mv	https://figshare.com/articles/journal_contribution/Biallelic_i_i_i_NAA60_i_variants_with_impaired_N-terminal_acetylation_capacity_cause_autosomal_recessive_primary_familial_brain_calcifications/26508340
dc.rights.none.fl_str_mv	CC BY 4.0 info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv	Biological sciences Genetics Biomedical and clinical sciences Neurosciences Acetylation Disease genetics Mechanisms of disease Movement disorders
dc.title.none.fl_str_mv	Biallelic <i> </i><i>NAA60</i> variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications
dc.type.none.fl_str_mv	Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal
description	<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>
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id	Manara2_d1dd325b0475d0d4976da78d248a636d
identifier_str_mv	10.1038/s41467-024-46354-0
network_acronym_str	Manara2
network_name_str	Manara2
oai_identifier_str	oai:figshare.com:article/26508340
publishDate	2024
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rights_invalid_str_mv	CC BY 4.0
spelling	Biallelic <i> </i><i>NAA60</i> variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcificationsViorica Chelban (4569337)Henriette Aksnes (205652)Reza Maroofian (5237852)Lauren C. LaMonica (19342717)Luis Seabra (19342720)Anette Siggervåg (19342723)Perrine Devic (17843042)Hanan E. Shamseldin (8987366)Jana Vandrovcova (90909)David Murphy (483511)Anne-Claire Richard (3873238)Olivier Quenez (3282843)Antoine Bonnevalle (19342726)M. Natalia Zanetti (19342729)Rauan Kaiyrzhanov (11494177)Vincenzo Salpietro (4569352)Stephanie Efthymiou (4569349)Lucia V. Schottlaender (19342732)Heba Morsy (3485405)Annarita Scardamaglia (16423404)Ambreen Tariq (19342735)Alistair T. Pagnamenta (6380606)Ajia Pennavaria (19342738)Liv S. Krogstad (19342741)Åse K. Bekkelund (19342744)Alessia Caiella (19342747)Nina Glomnes (205655)Kirsten M. Brønstad (19342750)Sandrine Tury (5812580)Andrés Moreno De Luca (19342753)Anne Boland-Auge (8536302)Robert Olaso (82489)Jean-François Deleuze (3626111)Mathieu Anheim (241061)Benjamin Cretin (303294)Barbara Vona (5237843)Fahad Alajlan (18078073)Firdous Abdulwahab (3485432)Jean-Luc Battini (19342756)Rojan İpek (19342759)Peter Bauer (524851)Giovanni Zifarelli (17487201)Serdal Gungor (13015697)Semra Hiz Kurul (19342762)Hanns Lochmuller (5280071)Sahar I. Da’as (9631717)Khalid A. Fakhro (3158862)Alicia Gómez-Pascual (15250291)Juan A. Botía (7947932)Nicholas W. Wood (49276)Rita Horvath (4474222)Andreas M. Ernst (19342765)James E. Rothman (369943)Meriel McEntagart (2636713)Yanick J. Crow (9433775)Fowzan S. Alkuraya (8791703)Gaël Nicolas (3873235)SYNaPS Study Group (19342768)Henry Houlden (110428)Thomas Arnesen (109198)Biological sciencesGeneticsBiomedical and clinical sciencesNeurosciencesAcetylationDisease geneticsMechanisms of diseaseMovement disorders<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>2024-03-13T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41467-024-46354-0https://figshare.com/articles/journal_contribution/Biallelic_i_i_i_NAA60_i_variants_with_impaired_N-terminal_acetylation_capacity_cause_autosomal_recessive_primary_familial_brain_calcifications/26508340CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/265083402024-03-13T09:00:00Z
spellingShingle	Biallelic <i> </i><i>NAA60</i> variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications Viorica Chelban (4569337) Biological sciences Genetics Biomedical and clinical sciences Neurosciences Acetylation Disease genetics Mechanisms of disease Movement disorders
status_str	publishedVersion
title	Biallelic <i> </i><i>NAA60</i> variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications
title_full	Biallelic <i> </i><i>NAA60</i> variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications
title_fullStr	Biallelic <i> </i><i>NAA60</i> variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications
title_full_unstemmed	Biallelic <i> </i><i>NAA60</i> variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications
title_short	Biallelic <i> </i><i>NAA60</i> variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications
title_sort	Biallelic <i> </i><i>NAA60</i> variants with impaired N-terminal acetylation capacity cause autosomal recessive primary familial brain calcifications
topic	Biological sciences Genetics Biomedical and clinical sciences Neurosciences Acetylation Disease genetics Mechanisms of disease Movement disorders

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

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