Clinical and Molecular Spectrum of Autosomal Recessive CA8-Related Cerebellar Ataxia

Background: Based on a limited number of reported families, biallelic CA8 variants have currently been associated with a recessive neurological disorder named, cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CAMRQ-3). Objectives: We aim to comprehensively investigate CA8-relate...

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Autores: Kaiyrzhanov R, Ortigoza-Escobar JD, Stringer BW, Ganieva M, Gowda VK, Srinivasan VM, Macaya A, Laner A, Onbool E, Al-Shammari R, Al-Owain M, Deconinck N, Vilain C, Dontaine P, Self E, Akram R, Hussain G, Baig SM, Iqbal J, Salpietro V, Neshatdoust M, Kasiri M, Yesil G, Uygur T, Pysden K, Berry IR, Alves CA, Giacomotto J, Houlden H, Maroofian R
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p26153
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=26153
Access Level:acceso abierto
Palabra clave:CA8
ataxia
cerebellar atrophy
vermis atrophy
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spelling Clinical and Molecular Spectrum of Autosomal Recessive CA8-Related Cerebellar AtaxiaKaiyrzhanov ROrtigoza-Escobar JDStringer BWGanieva MGowda VKSrinivasan VMMacaya ALaner AOnbool EAl-Shammari RAl-Owain MDeconinck NVilain CDontaine PSelf EAkram RHussain GBaig SMIqbal JSalpietro VNeshatdoust MKasiri MYesil GUygur TPysden KBerry IRAlves CAGiacomotto JHoulden HMaroofian RCA8ataxiacerebellar atrophyvermis atrophyBackground: Based on a limited number of reported families, biallelic CA8 variants have currently been associated with a recessive neurological disorder named, cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CAMRQ-3). Objectives: We aim to comprehensively investigate CA8-related disorders (CA8-RD) by reviewing existing literature and exploring neurological, neuroradiological, and molecular observations in a cohort of newly identified patients. Methods: We analyzed the phenotype of 27 affected individuals from 14 families with biallelic CA8 variants (including data from 15 newly identified patients from eight families), ages 4 to 35 years. Clinical, genetic, and radiological assessments were performed, and zebrafish models with ca8 knockout were used for functional analysis. Results: Patients exhibited varying degrees of neurodevelopmental disorders (NDD), along with predominantly progressive cerebellar ataxia and pyramidal signs and variable bradykinesia, dystonia, and sensory impairment. Quadrupedal gait was present in only 10 of 27 patients. Progressive selective cerebellar atrophy, predominantly affecting the superior vermis, was a key diagnostic finding in all patients. Seven novel homozygous CA8 variants were identified. Zebrafish models demonstrated impaired early neurodevelopment and motor behavior on ca8 knockout. Conclusion: Our comprehensive analysis of phenotypic features indicates that CA8-RD exhibits a wide range of clinical manifestations, setting it apart from other subtypes within the category of CAMRQ. CA8-RD is characterized by cerebellar atrophy and should be recognized as part of the autosomal-recessive cerebellar ataxias associated with NDD. Notably, the presence of progressive superior vermis atrophy serves as a valuable diagnostic indicator. (c) 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.WILEY2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=26153MOVEMENT DISORDERSISSN: 08853185ISSNe: 15318257reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p261532026-05-27T12:37:41Z
dc.title.none.fl_str_mv Clinical and Molecular Spectrum of Autosomal Recessive CA8-Related Cerebellar Ataxia
title Clinical and Molecular Spectrum of Autosomal Recessive CA8-Related Cerebellar Ataxia
spellingShingle Clinical and Molecular Spectrum of Autosomal Recessive CA8-Related Cerebellar Ataxia
Kaiyrzhanov R
CA8
ataxia
cerebellar atrophy
vermis atrophy
title_short Clinical and Molecular Spectrum of Autosomal Recessive CA8-Related Cerebellar Ataxia
title_full Clinical and Molecular Spectrum of Autosomal Recessive CA8-Related Cerebellar Ataxia
title_fullStr Clinical and Molecular Spectrum of Autosomal Recessive CA8-Related Cerebellar Ataxia
title_full_unstemmed Clinical and Molecular Spectrum of Autosomal Recessive CA8-Related Cerebellar Ataxia
title_sort Clinical and Molecular Spectrum of Autosomal Recessive CA8-Related Cerebellar Ataxia
dc.creator.none.fl_str_mv Kaiyrzhanov R
Ortigoza-Escobar JD
Stringer BW
Ganieva M
Gowda VK
Srinivasan VM
Macaya A
Laner A
Onbool E
Al-Shammari R
Al-Owain M
Deconinck N
Vilain C
Dontaine P
Self E
Akram R
Hussain G
Baig SM
Iqbal J
Salpietro V
Neshatdoust M
Kasiri M
Yesil G
Uygur T
Pysden K
Berry IR
Alves CA
Giacomotto J
Houlden H
Maroofian R
author Kaiyrzhanov R
author_facet Kaiyrzhanov R
Ortigoza-Escobar JD
Stringer BW
Ganieva M
Gowda VK
Srinivasan VM
Macaya A
Laner A
Onbool E
Al-Shammari R
Al-Owain M
Deconinck N
Vilain C
Dontaine P
Self E
Akram R
Hussain G
Baig SM
Iqbal J
Salpietro V
Neshatdoust M
Kasiri M
Yesil G
Uygur T
Pysden K
Berry IR
Alves CA
Giacomotto J
Houlden H
Maroofian R
author_role author
author2 Ortigoza-Escobar JD
Stringer BW
Ganieva M
Gowda VK
Srinivasan VM
Macaya A
Laner A
Onbool E
Al-Shammari R
Al-Owain M
Deconinck N
Vilain C
Dontaine P
Self E
Akram R
Hussain G
Baig SM
Iqbal J
Salpietro V
Neshatdoust M
Kasiri M
Yesil G
Uygur T
Pysden K
Berry IR
Alves CA
Giacomotto J
Houlden H
Maroofian R
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
dc.subject.none.fl_str_mv CA8
ataxia
cerebellar atrophy
vermis atrophy
topic CA8
ataxia
cerebellar atrophy
vermis atrophy
description Background: Based on a limited number of reported families, biallelic CA8 variants have currently been associated with a recessive neurological disorder named, cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CAMRQ-3). Objectives: We aim to comprehensively investigate CA8-related disorders (CA8-RD) by reviewing existing literature and exploring neurological, neuroradiological, and molecular observations in a cohort of newly identified patients. Methods: We analyzed the phenotype of 27 affected individuals from 14 families with biallelic CA8 variants (including data from 15 newly identified patients from eight families), ages 4 to 35 years. Clinical, genetic, and radiological assessments were performed, and zebrafish models with ca8 knockout were used for functional analysis. Results: Patients exhibited varying degrees of neurodevelopmental disorders (NDD), along with predominantly progressive cerebellar ataxia and pyramidal signs and variable bradykinesia, dystonia, and sensory impairment. Quadrupedal gait was present in only 10 of 27 patients. Progressive selective cerebellar atrophy, predominantly affecting the superior vermis, was a key diagnostic finding in all patients. Seven novel homozygous CA8 variants were identified. Zebrafish models demonstrated impaired early neurodevelopment and motor behavior on ca8 knockout. Conclusion: Our comprehensive analysis of phenotypic features indicates that CA8-RD exhibits a wide range of clinical manifestations, setting it apart from other subtypes within the category of CAMRQ. CA8-RD is characterized by cerebellar atrophy and should be recognized as part of the autosomal-recessive cerebellar ataxias associated with NDD. Notably, the presence of progressive superior vermis atrophy serves as a valuable diagnostic indicator. (c) 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=26153
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=26153
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv WILEY
publisher.none.fl_str_mv WILEY
dc.source.none.fl_str_mv MOVEMENT DISORDERS
ISSN: 08853185
ISSNe: 15318257
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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