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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 principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570320/ https://www.ncbi.nlm.nih.gov/pubmed/36233161 http://dx.doi.org/10.3390/ijms231911847 |
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author | Martínez-Rubio, Dolores Hinarejos, Isabel Sancho, Paula Gorría-Redondo, Nerea Bernadó-Fonz, Raquel Tello, Cristina Marco-Marín, Clara Martí-Carrera, 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 Gordo, Mar O’Callaghan 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_facet | Martínez-Rubio, Dolores Hinarejos, Isabel Sancho, Paula Gorría-Redondo, Nerea Bernadó-Fonz, Raquel Tello, Cristina Marco-Marín, Clara Martí-Carrera, 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 Gordo, Mar O’Callaghan 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_sort | Martínez-Rubio, Dolores |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-9570320 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95703202022-10-17 Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias Martínez-Rubio, Dolores Hinarejos, Isabel Sancho, Paula Gorría-Redondo, Nerea Bernadó-Fonz, Raquel Tello, Cristina Marco-Marín, Clara Martí-Carrera, 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 Gordo, Mar O’Callaghan 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 Int J Mol Sci Article 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. MDPI 2022-10-06 /pmc/articles/PMC9570320/ /pubmed/36233161 http://dx.doi.org/10.3390/ijms231911847 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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/). |
spellingShingle | Article Martínez-Rubio, Dolores Hinarejos, Isabel Sancho, Paula Gorría-Redondo, Nerea Bernadó-Fonz, Raquel Tello, Cristina Marco-Marín, Clara Martí-Carrera, 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 Gordo, Mar O’Callaghan 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 Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias |
title | 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_short | Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias |
title_sort | mutations, genes, and phenotypes related to movement disorders and ataxias |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570320/ https://www.ncbi.nlm.nih.gov/pubmed/36233161 http://dx.doi.org/10.3390/ijms231911847 |
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