Cargando…

Filamin A Variant as a Possible Second-Hit Gene Promoting Moyamoya Disease–like Vascular Formation Associated With RNF213 p.R4810K Variant

BACKGROUND AND OBJECTIVE: The objective of this case report was to identify a second-hit gene that may promote Moyamoya disease (MMD)–like vascular formation in an individual having the RNF213 p.R4810K variant. METHODS: We performed magnetic resonance imaging and genetic analyses of RNF213 and FLNA...

Descripción completa

Detalles Bibliográficos
Autores principales: Ikeuchi, Yasuhito, Kitayama, Jiro, Sahara, Noriyuki, Okata, Takuya, Miyake, Noriko, Matsumoto, Naomichi, Kitazono, Takanari, Ago, Tetsuro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465836/
https://www.ncbi.nlm.nih.gov/pubmed/36101542
http://dx.doi.org/10.1212/NXG.0000000000200017
_version_ 1784787877923651584
author Ikeuchi, Yasuhito
Kitayama, Jiro
Sahara, Noriyuki
Okata, Takuya
Miyake, Noriko
Matsumoto, Naomichi
Kitazono, Takanari
Ago, Tetsuro
author_facet Ikeuchi, Yasuhito
Kitayama, Jiro
Sahara, Noriyuki
Okata, Takuya
Miyake, Noriko
Matsumoto, Naomichi
Kitazono, Takanari
Ago, Tetsuro
author_sort Ikeuchi, Yasuhito
collection PubMed
description BACKGROUND AND OBJECTIVE: The objective of this case report was to identify a second-hit gene that may promote Moyamoya disease (MMD)–like vascular formation in an individual having the RNF213 p.R4810K variant. METHODS: We performed magnetic resonance imaging and genetic analyses of RNF213 and FLNA in a 21-year-old woman, who showed Ehlers-Danlos–like symptoms and developed a first-ever unprovoked seizure, and of her healthy parents. RESULTS: We identified bilateral periventricular nodular heterotopia (PNH) as the cause of seizures and MMD-like vascular formation in the patient. The patient had the RNF213 p.R4810K variant. Exome analysis identified c.4868delG in the X-linked FLNA gene encoding filamin A p.G1623V fs*41, which could explain PNH and Ehlers-Danlos–like symptoms. Her mother had the same FLNA variant and had asymptomatic bilateral PNH, whereas her father had the RNF213 variant and had normal cerebrovascular structure. DISCUSSION: The family study suggested that the FLNA variant promoted MMD-like vascular formation in a patient having the RNF213 variant, while the RNF213 variant amplified the phenotypic changes elicited by the FLNA abnormality. Collectively, we identified a gene abnormality in filamin A, a target of RNF213-mediated proteasomal degradation, that may promote MMD-like vascular formation as a possible second-hit gene in individuals having the RNF213 p.R4810K variant.
format Online
Article
Text
id pubmed-9465836
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Wolters Kluwer
record_format MEDLINE/PubMed
spelling pubmed-94658362022-09-12 Filamin A Variant as a Possible Second-Hit Gene Promoting Moyamoya Disease–like Vascular Formation Associated With RNF213 p.R4810K Variant Ikeuchi, Yasuhito Kitayama, Jiro Sahara, Noriyuki Okata, Takuya Miyake, Noriko Matsumoto, Naomichi Kitazono, Takanari Ago, Tetsuro Neurol Genet Clinical/Scientific Note BACKGROUND AND OBJECTIVE: The objective of this case report was to identify a second-hit gene that may promote Moyamoya disease (MMD)–like vascular formation in an individual having the RNF213 p.R4810K variant. METHODS: We performed magnetic resonance imaging and genetic analyses of RNF213 and FLNA in a 21-year-old woman, who showed Ehlers-Danlos–like symptoms and developed a first-ever unprovoked seizure, and of her healthy parents. RESULTS: We identified bilateral periventricular nodular heterotopia (PNH) as the cause of seizures and MMD-like vascular formation in the patient. The patient had the RNF213 p.R4810K variant. Exome analysis identified c.4868delG in the X-linked FLNA gene encoding filamin A p.G1623V fs*41, which could explain PNH and Ehlers-Danlos–like symptoms. Her mother had the same FLNA variant and had asymptomatic bilateral PNH, whereas her father had the RNF213 variant and had normal cerebrovascular structure. DISCUSSION: The family study suggested that the FLNA variant promoted MMD-like vascular formation in a patient having the RNF213 variant, while the RNF213 variant amplified the phenotypic changes elicited by the FLNA abnormality. Collectively, we identified a gene abnormality in filamin A, a target of RNF213-mediated proteasomal degradation, that may promote MMD-like vascular formation as a possible second-hit gene in individuals having the RNF213 p.R4810K variant. Wolters Kluwer 2022-09-09 /pmc/articles/PMC9465836/ /pubmed/36101542 http://dx.doi.org/10.1212/NXG.0000000000200017 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Clinical/Scientific Note
Ikeuchi, Yasuhito
Kitayama, Jiro
Sahara, Noriyuki
Okata, Takuya
Miyake, Noriko
Matsumoto, Naomichi
Kitazono, Takanari
Ago, Tetsuro
Filamin A Variant as a Possible Second-Hit Gene Promoting Moyamoya Disease–like Vascular Formation Associated With RNF213 p.R4810K Variant
title Filamin A Variant as a Possible Second-Hit Gene Promoting Moyamoya Disease–like Vascular Formation Associated With RNF213 p.R4810K Variant
title_full Filamin A Variant as a Possible Second-Hit Gene Promoting Moyamoya Disease–like Vascular Formation Associated With RNF213 p.R4810K Variant
title_fullStr Filamin A Variant as a Possible Second-Hit Gene Promoting Moyamoya Disease–like Vascular Formation Associated With RNF213 p.R4810K Variant
title_full_unstemmed Filamin A Variant as a Possible Second-Hit Gene Promoting Moyamoya Disease–like Vascular Formation Associated With RNF213 p.R4810K Variant
title_short Filamin A Variant as a Possible Second-Hit Gene Promoting Moyamoya Disease–like Vascular Formation Associated With RNF213 p.R4810K Variant
title_sort filamin a variant as a possible second-hit gene promoting moyamoya disease–like vascular formation associated with rnf213 p.r4810k variant
topic Clinical/Scientific Note
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9465836/
https://www.ncbi.nlm.nih.gov/pubmed/36101542
http://dx.doi.org/10.1212/NXG.0000000000200017
work_keys_str_mv AT ikeuchiyasuhito filaminavariantasapossiblesecondhitgenepromotingmoyamoyadiseaselikevascularformationassociatedwithrnf213pr4810kvariant
AT kitayamajiro filaminavariantasapossiblesecondhitgenepromotingmoyamoyadiseaselikevascularformationassociatedwithrnf213pr4810kvariant
AT saharanoriyuki filaminavariantasapossiblesecondhitgenepromotingmoyamoyadiseaselikevascularformationassociatedwithrnf213pr4810kvariant
AT okatatakuya filaminavariantasapossiblesecondhitgenepromotingmoyamoyadiseaselikevascularformationassociatedwithrnf213pr4810kvariant
AT miyakenoriko filaminavariantasapossiblesecondhitgenepromotingmoyamoyadiseaselikevascularformationassociatedwithrnf213pr4810kvariant
AT matsumotonaomichi filaminavariantasapossiblesecondhitgenepromotingmoyamoyadiseaselikevascularformationassociatedwithrnf213pr4810kvariant
AT kitazonotakanari filaminavariantasapossiblesecondhitgenepromotingmoyamoyadiseaselikevascularformationassociatedwithrnf213pr4810kvariant
AT agotetsuro filaminavariantasapossiblesecondhitgenepromotingmoyamoyadiseaselikevascularformationassociatedwithrnf213pr4810kvariant