Cargando…

Abnormal Paraplegin Expression in Swollen Neurites, τ- and α-Synuclein Pathology in a Case of Hereditary Spastic Paraplegia SPG7 with an Ala510Val Mutation

Mutations in the SPG7 gene are the most frequent cause of autosomal recessive hereditary spastic paraplegias and spastic ataxias. Ala510Val is the most common SPG7 mutation, with a frequency of up to 1% in the general population. Here we report the clinical, genetic, and neuropathological findings i...

Descripción completa

Detalles Bibliográficos
Autores principales: Thal, Dietmar R., Züchner, Stephan, Gierer, Stephan, Schulte, Claudia, Schöls, Ludger, Schüle, Rebecca, Synofzik, Matthis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632789/
https://www.ncbi.nlm.nih.gov/pubmed/26506339
http://dx.doi.org/10.3390/ijms161025050
_version_ 1782399097042370560
author Thal, Dietmar R.
Züchner, Stephan
Gierer, Stephan
Schulte, Claudia
Schöls, Ludger
Schüle, Rebecca
Synofzik, Matthis
author_facet Thal, Dietmar R.
Züchner, Stephan
Gierer, Stephan
Schulte, Claudia
Schöls, Ludger
Schüle, Rebecca
Synofzik, Matthis
author_sort Thal, Dietmar R.
collection PubMed
description Mutations in the SPG7 gene are the most frequent cause of autosomal recessive hereditary spastic paraplegias and spastic ataxias. Ala510Val is the most common SPG7 mutation, with a frequency of up to 1% in the general population. Here we report the clinical, genetic, and neuropathological findings in a homozygous Ala510Val SPG7 case with spastic ataxia. Neuron loss with associated gliosis was found in the inferior olivary nucleus, the dentate nucleus of the cerebellum, the substantia nigra and the basal nucleus of Meynert. Neurofilament and/or paraplegin accumulation was observed in swollen neurites in the cerebellar and cerebral cortex. This case also showed subcortical τ-pathology in an unique distribution pattern largely restricted to the brainstem. α-synuclein containing Lewy bodies (LBs) were observed in the brainstem and the cortex, compatible with a limbic pattern of Braak LB-Disease stage 4. Taken together, this case shows that the spectrum of pathologies in SPG7 can include neuron loss of the dentate nucleus and the inferior olivary nucleus as well as neuritic pathology. The progressive supranuclear palsy-like brainstem predominant pattern of τ pathology and α-synuclein containing Lewy bodies in our SPG7 cases may be either coincidental or related to SPG7 in addition to neuron loss and neuritic pathology.
format Online
Article
Text
id pubmed-4632789
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-46327892015-11-23 Abnormal Paraplegin Expression in Swollen Neurites, τ- and α-Synuclein Pathology in a Case of Hereditary Spastic Paraplegia SPG7 with an Ala510Val Mutation Thal, Dietmar R. Züchner, Stephan Gierer, Stephan Schulte, Claudia Schöls, Ludger Schüle, Rebecca Synofzik, Matthis Int J Mol Sci Article Mutations in the SPG7 gene are the most frequent cause of autosomal recessive hereditary spastic paraplegias and spastic ataxias. Ala510Val is the most common SPG7 mutation, with a frequency of up to 1% in the general population. Here we report the clinical, genetic, and neuropathological findings in a homozygous Ala510Val SPG7 case with spastic ataxia. Neuron loss with associated gliosis was found in the inferior olivary nucleus, the dentate nucleus of the cerebellum, the substantia nigra and the basal nucleus of Meynert. Neurofilament and/or paraplegin accumulation was observed in swollen neurites in the cerebellar and cerebral cortex. This case also showed subcortical τ-pathology in an unique distribution pattern largely restricted to the brainstem. α-synuclein containing Lewy bodies (LBs) were observed in the brainstem and the cortex, compatible with a limbic pattern of Braak LB-Disease stage 4. Taken together, this case shows that the spectrum of pathologies in SPG7 can include neuron loss of the dentate nucleus and the inferior olivary nucleus as well as neuritic pathology. The progressive supranuclear palsy-like brainstem predominant pattern of τ pathology and α-synuclein containing Lewy bodies in our SPG7 cases may be either coincidental or related to SPG7 in addition to neuron loss and neuritic pathology. MDPI 2015-10-21 /pmc/articles/PMC4632789/ /pubmed/26506339 http://dx.doi.org/10.3390/ijms161025050 Text en © 2015 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 license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Thal, Dietmar R.
Züchner, Stephan
Gierer, Stephan
Schulte, Claudia
Schöls, Ludger
Schüle, Rebecca
Synofzik, Matthis
Abnormal Paraplegin Expression in Swollen Neurites, τ- and α-Synuclein Pathology in a Case of Hereditary Spastic Paraplegia SPG7 with an Ala510Val Mutation
title Abnormal Paraplegin Expression in Swollen Neurites, τ- and α-Synuclein Pathology in a Case of Hereditary Spastic Paraplegia SPG7 with an Ala510Val Mutation
title_full Abnormal Paraplegin Expression in Swollen Neurites, τ- and α-Synuclein Pathology in a Case of Hereditary Spastic Paraplegia SPG7 with an Ala510Val Mutation
title_fullStr Abnormal Paraplegin Expression in Swollen Neurites, τ- and α-Synuclein Pathology in a Case of Hereditary Spastic Paraplegia SPG7 with an Ala510Val Mutation
title_full_unstemmed Abnormal Paraplegin Expression in Swollen Neurites, τ- and α-Synuclein Pathology in a Case of Hereditary Spastic Paraplegia SPG7 with an Ala510Val Mutation
title_short Abnormal Paraplegin Expression in Swollen Neurites, τ- and α-Synuclein Pathology in a Case of Hereditary Spastic Paraplegia SPG7 with an Ala510Val Mutation
title_sort abnormal paraplegin expression in swollen neurites, τ- and α-synuclein pathology in a case of hereditary spastic paraplegia spg7 with an ala510val mutation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632789/
https://www.ncbi.nlm.nih.gov/pubmed/26506339
http://dx.doi.org/10.3390/ijms161025050
work_keys_str_mv AT thaldietmarr abnormalparapleginexpressioninswollenneuritestandasynucleinpathologyinacaseofhereditaryspasticparaplegiaspg7withanala510valmutation
AT zuchnerstephan abnormalparapleginexpressioninswollenneuritestandasynucleinpathologyinacaseofhereditaryspasticparaplegiaspg7withanala510valmutation
AT giererstephan abnormalparapleginexpressioninswollenneuritestandasynucleinpathologyinacaseofhereditaryspasticparaplegiaspg7withanala510valmutation
AT schulteclaudia abnormalparapleginexpressioninswollenneuritestandasynucleinpathologyinacaseofhereditaryspasticparaplegiaspg7withanala510valmutation
AT scholsludger abnormalparapleginexpressioninswollenneuritestandasynucleinpathologyinacaseofhereditaryspasticparaplegiaspg7withanala510valmutation
AT schulerebecca abnormalparapleginexpressioninswollenneuritestandasynucleinpathologyinacaseofhereditaryspasticparaplegiaspg7withanala510valmutation
AT synofzikmatthis abnormalparapleginexpressioninswollenneuritestandasynucleinpathologyinacaseofhereditaryspasticparaplegiaspg7withanala510valmutation