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Heterozygous PLA2G6 Mutation Leads to Iron Accumulation Within Basal Ganglia and Parkinson's Disease

Mutations of PLA2G6 gene are responsible for PARK14, an autosomal recessive L-DOPA responsive dystonia/parkinsonism with early/adult onset. This phenotype possesses an high clinical variability, which consists in the occurrence of cerebral and cerebellar atrophy, iron accumulation in the basal gangl...

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Autores principales: Ferese, Rosangela, Scala, Simona, Biagioni, Francesca, Giardina, Emiliano, Zampatti, Stefania, Modugno, Nicola, Colonnese, Claudio, Storto, Marianna, Fornai, Francesco, Novelli, Giuseppe, Ruggieri, Stefano, Gambardella, Stefano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048271/
https://www.ncbi.nlm.nih.gov/pubmed/30042723
http://dx.doi.org/10.3389/fneur.2018.00536
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author Ferese, Rosangela
Scala, Simona
Biagioni, Francesca
Giardina, Emiliano
Zampatti, Stefania
Modugno, Nicola
Colonnese, Claudio
Storto, Marianna
Fornai, Francesco
Novelli, Giuseppe
Ruggieri, Stefano
Gambardella, Stefano
author_facet Ferese, Rosangela
Scala, Simona
Biagioni, Francesca
Giardina, Emiliano
Zampatti, Stefania
Modugno, Nicola
Colonnese, Claudio
Storto, Marianna
Fornai, Francesco
Novelli, Giuseppe
Ruggieri, Stefano
Gambardella, Stefano
author_sort Ferese, Rosangela
collection PubMed
description Mutations of PLA2G6 gene are responsible for PARK14, an autosomal recessive L-DOPA responsive dystonia/parkinsonism with early/adult onset. This phenotype possesses an high clinical variability, which consists in the occurrence of cerebral and cerebellar atrophy, iron accumulation in the basal ganglia, and cognitive decline. This report describes a PD patient carrying an heterozygous PLA2G6 mutation, which was identified also in his PD affected sister. This patient is characterized by a L-DOPA responsive typical parkinsonian syndrome without the occurrence of dystonia, a slight cognitive decline, presence of iron accumulation both in neo and paleostriatum while cerebellar atrophy was absent. Clinical and imaging features are compatible with the PARK14 phenotype. Although PARK14 has been previously reported to be inherited as a recessive disorder, clinical and genetic analysis of this proband and his family rise the hypothesis that even heterozygous PLA2G6 mutations may cause PARK14. It remains to be analyzed whether these heterozygous variants may act as dominant mutations, or they merely increase the risk to develop PD by acting within a context of synergistic genetic and/or environmental backgrounds.
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spelling pubmed-60482712018-07-24 Heterozygous PLA2G6 Mutation Leads to Iron Accumulation Within Basal Ganglia and Parkinson's Disease Ferese, Rosangela Scala, Simona Biagioni, Francesca Giardina, Emiliano Zampatti, Stefania Modugno, Nicola Colonnese, Claudio Storto, Marianna Fornai, Francesco Novelli, Giuseppe Ruggieri, Stefano Gambardella, Stefano Front Neurol Neurology Mutations of PLA2G6 gene are responsible for PARK14, an autosomal recessive L-DOPA responsive dystonia/parkinsonism with early/adult onset. This phenotype possesses an high clinical variability, which consists in the occurrence of cerebral and cerebellar atrophy, iron accumulation in the basal ganglia, and cognitive decline. This report describes a PD patient carrying an heterozygous PLA2G6 mutation, which was identified also in his PD affected sister. This patient is characterized by a L-DOPA responsive typical parkinsonian syndrome without the occurrence of dystonia, a slight cognitive decline, presence of iron accumulation both in neo and paleostriatum while cerebellar atrophy was absent. Clinical and imaging features are compatible with the PARK14 phenotype. Although PARK14 has been previously reported to be inherited as a recessive disorder, clinical and genetic analysis of this proband and his family rise the hypothesis that even heterozygous PLA2G6 mutations may cause PARK14. It remains to be analyzed whether these heterozygous variants may act as dominant mutations, or they merely increase the risk to develop PD by acting within a context of synergistic genetic and/or environmental backgrounds. Frontiers Media S.A. 2018-07-10 /pmc/articles/PMC6048271/ /pubmed/30042723 http://dx.doi.org/10.3389/fneur.2018.00536 Text en Copyright © 2018 Ferese, Scala, Biagioni, Giardina, Zampatti, Modugno, Colonnese, Storto, Fornai, Novelli, Ruggieri and Gambardella. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Ferese, Rosangela
Scala, Simona
Biagioni, Francesca
Giardina, Emiliano
Zampatti, Stefania
Modugno, Nicola
Colonnese, Claudio
Storto, Marianna
Fornai, Francesco
Novelli, Giuseppe
Ruggieri, Stefano
Gambardella, Stefano
Heterozygous PLA2G6 Mutation Leads to Iron Accumulation Within Basal Ganglia and Parkinson's Disease
title Heterozygous PLA2G6 Mutation Leads to Iron Accumulation Within Basal Ganglia and Parkinson's Disease
title_full Heterozygous PLA2G6 Mutation Leads to Iron Accumulation Within Basal Ganglia and Parkinson's Disease
title_fullStr Heterozygous PLA2G6 Mutation Leads to Iron Accumulation Within Basal Ganglia and Parkinson's Disease
title_full_unstemmed Heterozygous PLA2G6 Mutation Leads to Iron Accumulation Within Basal Ganglia and Parkinson's Disease
title_short Heterozygous PLA2G6 Mutation Leads to Iron Accumulation Within Basal Ganglia and Parkinson's Disease
title_sort heterozygous pla2g6 mutation leads to iron accumulation within basal ganglia and parkinson's disease
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048271/
https://www.ncbi.nlm.nih.gov/pubmed/30042723
http://dx.doi.org/10.3389/fneur.2018.00536
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