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...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universidad del País Vasco |
| Repositorio: | Addi. Archivo Digital para la Docencia y la Investigación |
| OAI Identifier: | oai:addi.ehu.eus:10810/58251 |
| Acceso en línea: | http://hdl.handle.net/10810/58251 |
| 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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Mutations, Genes, and Phenotypes Related to Movement Disorders and AtaxiasMartínez Rubio, DoloresHinarejos, IsabelSancho, PaulaGorría Redondo, NereaBernadó Fonz, RaquelTello, CristinaMarco Marín, ClaraMartí Carrera, María ItxasoMartínez González, María JesúsGarcía Ribes, AinhoaBaviera Muñoz, RaquelSastre Bataller, IsabelMartínez Torres, IreneDuat Rodríguez, AnnaJaneiro, PatríciaMoreno, EstherPías Peleteiro, LeticiaO’Callaghan Gordo, MarRuiz Gómez, ÁngelesMuñoz, EstebanMartí, Maria JosepSánchez Monteagudo, AnaFuster, CandelaAndrés Bordería, AmparoPons, Roser MariaJesús Maestre, SilviaMir, PabloLupo, VincenzoPérez Dueñas, BelénDarling, AlejandraAguilera Albesa, SergioEspinós, Carmenmovement 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.This work was supported by the Instituto de Salud Carlos III (ISCIII)—Subdirección General de Evaluación y Fomento de la Investigación within the framework of the National R + D+I Plan co-funded with European Regional Development Funds (ERDF) [Grants PI18/00147 and PI21/00103 to CE]; the Fundació La Marató TV3 [Grants 20143130 and 20143131 to BPD and CE]; and by the Generalitat Valenciana [Grant PROMETEO/2018/135 to CE]. Part of the equipment employed in this work was funded by Generalitat Valenciana and co-financed with ERDF (OP ERDF of Comunitat Valenciana 2014–2020). PS had an FPU-PhD fellowship funded by the Spanish Ministry of Education, Culture and Sport [FPU15/00964]. IH has a PFIS-PhD fellowship [FI19/00072]. ASM has a contract funded by the Spanish Foundation Per Amor a l’Art (FPAA).MDPI2022202220222022info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/58251reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoInglésinfo:eu-repo/grantAgreement/MICIU/FPU15/00964https://www.mdpi.com/1422-0067/23/19/11847info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/© 2022 by the authors.Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/).oai:addi.ehu.eus:10810/582512026-06-18T09:23:17Z |
| 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, Dolores 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, Dolores Hinarejos, Isabel Sancho, Paula Gorría Redondo, Nerea Bernadó Fonz, Raquel Tello, Cristina Marco Marín, Clara Martí Carrera, María Itxaso Martínez González, María Jesús García Ribes, Ainhoa Baviera Muñoz, Raquel Sastre Bataller, Isabel Martínez Torres, Irene Duat Rodríguez, Anna Janeiro, Patrícia Moreno, Esther Pías Peleteiro, Leticia O’Callaghan Gordo, Mar Ruiz Gómez, Ángeles Muñoz, Esteban Martí, Maria Josep Sánchez Monteagudo, Ana Fuster, Candela Andrés Bordería, Amparo Pons, Roser Maria Jesús Maestre, Silvia Mir, Pablo Lupo, Vincenzo Pérez Dueñas, Belén Darling, Alejandra Aguilera Albesa, Sergio Espinós, Carmen |
| author |
Martínez Rubio, Dolores |
| author_facet |
Martínez Rubio, Dolores Hinarejos, Isabel Sancho, Paula Gorría Redondo, Nerea Bernadó Fonz, Raquel Tello, Cristina Marco Marín, Clara Martí Carrera, María Itxaso Martínez González, María Jesús García Ribes, Ainhoa Baviera Muñoz, Raquel Sastre Bataller, Isabel Martínez Torres, Irene Duat Rodríguez, Anna Janeiro, Patrícia Moreno, Esther Pías Peleteiro, Leticia O’Callaghan Gordo, Mar Ruiz Gómez, Ángeles Muñoz, Esteban Martí, Maria Josep Sánchez Monteagudo, Ana Fuster, Candela Andrés Bordería, Amparo Pons, Roser Maria Jesús Maestre, Silvia Mir, Pablo Lupo, Vincenzo Pérez Dueñas, Belén Darling, Alejandra Aguilera Albesa, Sergio Espinós, Carmen |
| author_role |
author |
| author2 |
Hinarejos, Isabel Sancho, Paula Gorría Redondo, Nerea Bernadó Fonz, Raquel Tello, Cristina Marco Marín, Clara Martí Carrera, María Itxaso Martínez González, María Jesús García Ribes, Ainhoa Baviera Muñoz, Raquel Sastre Bataller, Isabel Martínez Torres, Irene Duat Rodríguez, Anna Janeiro, Patrícia Moreno, Esther Pías Peleteiro, Leticia O’Callaghan Gordo, Mar Ruiz Gómez, Ángeles Muñoz, Esteban Martí, Maria Josep Sánchez Monteagudo, Ana Fuster, Candela Andrés Bordería, Amparo Pons, Roser Maria Jesús Maestre, Silvia Mir, Pablo Lupo, Vincenzo Pérez Dueñas, Belén Darling, Alejandra Aguilera Albesa, Sergio Espinós, Carmen |
| 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 2022 2022 2022 |
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info:eu-repo/semantics/article |
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article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10810/58251 |
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http://hdl.handle.net/10810/58251 |
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Inglés |
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Inglés |
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info:eu-repo/grantAgreement/MICIU/FPU15/00964 https://www.mdpi.com/1422-0067/23/19/11847 |
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info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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http://creativecommons.org/licenses/by/4.0/ |
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application/pdf |
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