Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias

Our clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are accepted, although isolated cases compatible with abnormal brain iron deposits...

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Autores: Martínez-Rubio D, Hinarejos I, Sancho P, Gorría-Redondo N, Bernadó-Fonz R, Tello C, Marco-Marín C, Martí-Carrera I, Martínez-González MJ, García-Ribes A, Baviera-Muñoz R, Sastre-Bataller I, Martínez-Torres I, Duat-Rodríguez A, Janeiro P, Moreno E, Pías-Peleteiro L, Gordo MO, Ruiz-Gómez Á, Muñoz E, Martí MJ, Sánchez-Monteagudo A, Fuster C, Andrés-Bordería A, Pons RM, Jesús-Maestre S, Mir P, Lupo V, Pérez-Dueñas B, Darling A, Aguilera-Albesa S, Espinós C
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
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:p22267
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=22267
Access Level:acceso abierto
Palabra clave:movement disorders
ataxia
cerebellar atrophy
neurodegeneration with brain iron accumulation (NBIA)
gene panel
exome sequencing
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spelling Mutations, Genes, and Phenotypes Related to Movement Disorders and AtaxiasMartínez-Rubio DHinarejos ISancho PGorría-Redondo NBernadó-Fonz RTello CMarco-Marín CMartí-Carrera IMartínez-González MJGarcía-Ribes ABaviera-Muñoz RSastre-Bataller IMartínez-Torres IDuat-Rodríguez AJaneiro PMoreno EPías-Peleteiro LGordo MORuiz-Gómez ÁMuñoz EMartí MJSánchez-Monteagudo AFuster CAndrés-Bordería APons RMJesús-Maestre SMir PLupo VPérez-Dueñas BDarling AAguilera-Albesa SEspinós Cmovement disordersataxiacerebellar atrophyneurodegeneration with brain iron accumulation (NBIA)gene panelexome sequencingOur clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are accepted, although isolated cases compatible with abnormal brain iron deposits are known. The patients were evaluated using standardised clinical assessments of ataxia and MDs. First, NBIA genes were analysed by Sanger sequencing and 59 patients achieved a diagnosis, including the detection of the founder mutation PANK2 p.T528M in Romani people. Then, we used a custom panel MovDisord and/or exome sequencing; 29 cases were solved with a great genetic heterogeneity (34 different mutations in 23 genes). Three patients presented brain iron deposits with Fe-sensitive MRI sequences and mutations in FBXO7, GLB1, and KIF1A, suggesting an NBIA-like phenotype. Eleven patients showed very early-onset ataxia and CA with cortical hyperintensities caused by mutations in ITPR1, KIF1A, SPTBN2, PLA2G6, PMPCA, and PRDX3. The novel variants were investigated by structural modelling, luciferase analysis, transcript/minigenes studies, or immunofluorescence assays. Our findings expand the phenotypes and the genetics of MDs and ataxias with early-onset CA and cortical hyperintensities and highlight that the abnormal brain iron accumulation or early cerebellar gliosis may resembling an NBIA phenotype.MDPI2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=22267INTERNATIONAL JOURNAL OF MOLECULAR SCIENCESISSN: 16616596ISSNe: 14220067reponame: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:p222672026-05-27T12:37:41Z
dc.title.none.fl_str_mv Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias
title Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias
spellingShingle Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias
Martínez-Rubio D
movement disorders
ataxia
cerebellar atrophy
neurodegeneration with brain iron accumulation (NBIA)
gene panel
exome sequencing
title_short Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias
title_full Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias
title_fullStr Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias
title_full_unstemmed Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias
title_sort Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias
dc.creator.none.fl_str_mv Martínez-Rubio D
Hinarejos I
Sancho P
Gorría-Redondo N
Bernadó-Fonz R
Tello C
Marco-Marín C
Martí-Carrera I
Martínez-González MJ
García-Ribes A
Baviera-Muñoz R
Sastre-Bataller I
Martínez-Torres I
Duat-Rodríguez A
Janeiro P
Moreno E
Pías-Peleteiro L
Gordo MO
Ruiz-Gómez Á
Muñoz E
Martí MJ
Sánchez-Monteagudo A
Fuster C
Andrés-Bordería A
Pons RM
Jesús-Maestre S
Mir P
Lupo V
Pérez-Dueñas B
Darling A
Aguilera-Albesa S
Espinós C
author Martínez-Rubio D
author_facet Martínez-Rubio D
Hinarejos I
Sancho P
Gorría-Redondo N
Bernadó-Fonz R
Tello C
Marco-Marín C
Martí-Carrera I
Martínez-González MJ
García-Ribes A
Baviera-Muñoz R
Sastre-Bataller I
Martínez-Torres I
Duat-Rodríguez A
Janeiro P
Moreno E
Pías-Peleteiro L
Gordo MO
Ruiz-Gómez Á
Muñoz E
Martí MJ
Sánchez-Monteagudo A
Fuster C
Andrés-Bordería A
Pons RM
Jesús-Maestre S
Mir P
Lupo V
Pérez-Dueñas B
Darling A
Aguilera-Albesa S
Espinós C
author_role author
author2 Hinarejos I
Sancho P
Gorría-Redondo N
Bernadó-Fonz R
Tello C
Marco-Marín C
Martí-Carrera I
Martínez-González MJ
García-Ribes A
Baviera-Muñoz R
Sastre-Bataller I
Martínez-Torres I
Duat-Rodríguez A
Janeiro P
Moreno E
Pías-Peleteiro L
Gordo MO
Ruiz-Gómez Á
Muñoz E
Martí MJ
Sánchez-Monteagudo A
Fuster C
Andrés-Bordería A
Pons RM
Jesús-Maestre S
Mir P
Lupo V
Pérez-Dueñas B
Darling A
Aguilera-Albesa S
Espinós C
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
dc.subject.none.fl_str_mv movement disorders
ataxia
cerebellar atrophy
neurodegeneration with brain iron accumulation (NBIA)
gene panel
exome sequencing
topic movement disorders
ataxia
cerebellar atrophy
neurodegeneration with brain iron accumulation (NBIA)
gene panel
exome sequencing
description Our clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are accepted, although isolated cases compatible with abnormal brain iron deposits are known. The patients were evaluated using standardised clinical assessments of ataxia and MDs. First, NBIA genes were analysed by Sanger sequencing and 59 patients achieved a diagnosis, including the detection of the founder mutation PANK2 p.T528M in Romani people. Then, we used a custom panel MovDisord and/or exome sequencing; 29 cases were solved with a great genetic heterogeneity (34 different mutations in 23 genes). Three patients presented brain iron deposits with Fe-sensitive MRI sequences and mutations in FBXO7, GLB1, and KIF1A, suggesting an NBIA-like phenotype. Eleven patients showed very early-onset ataxia and CA with cortical hyperintensities caused by mutations in ITPR1, KIF1A, SPTBN2, PLA2G6, PMPCA, and PRDX3. The novel variants were investigated by structural modelling, luciferase analysis, transcript/minigenes studies, or immunofluorescence assays. Our findings expand the phenotypes and the genetics of MDs and ataxias with early-onset CA and cortical hyperintensities and highlight that the abnormal brain iron accumulation or early cerebellar gliosis may resembling an NBIA phenotype.
publishDate 2022
dc.date.none.fl_str_mv 2022
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=22267
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=22267
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 MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN: 16616596
ISSNe: 14220067
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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score 15,811543

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