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Spinocerebellar ataxia 17: full phenotype in a 41 CAG/CAA repeats carrier

BACKGROUND: Spinocerebellar ataxia 17 (SCA17) is one of the most heterogeneous forms of autosomal dominant cerebellar ataxias with a large clinical spectrum which can mimic other movement disorders such as Huntington disease (HD), dystonia and parkinsonism. SCA17 is caused by an expansion of CAG/CAA...

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Autores principales: Origone, Paola, Gotta, Fabio, Lamp, Merit, Trevisan, Lucia, Geroldi, Alessandro, Massucco, Davide, Grazzini, Matteo, Massa, Federico, Ticconi, Flavia, Bauckneht, Matteo, Marchese, Roberta, Abbruzzese, Giovanni, Bellone, Emilia, Mandich, Paola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852964/
https://www.ncbi.nlm.nih.gov/pubmed/29564144
http://dx.doi.org/10.1186/s40673-018-0086-x
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author Origone, Paola
Gotta, Fabio
Lamp, Merit
Trevisan, Lucia
Geroldi, Alessandro
Massucco, Davide
Grazzini, Matteo
Massa, Federico
Ticconi, Flavia
Bauckneht, Matteo
Marchese, Roberta
Abbruzzese, Giovanni
Bellone, Emilia
Mandich, Paola
author_facet Origone, Paola
Gotta, Fabio
Lamp, Merit
Trevisan, Lucia
Geroldi, Alessandro
Massucco, Davide
Grazzini, Matteo
Massa, Federico
Ticconi, Flavia
Bauckneht, Matteo
Marchese, Roberta
Abbruzzese, Giovanni
Bellone, Emilia
Mandich, Paola
author_sort Origone, Paola
collection PubMed
description BACKGROUND: Spinocerebellar ataxia 17 (SCA17) is one of the most heterogeneous forms of autosomal dominant cerebellar ataxias with a large clinical spectrum which can mimic other movement disorders such as Huntington disease (HD), dystonia and parkinsonism. SCA17 is caused by an expansion of CAG/CAA repeat in the Tata binding protein (TBP) gene. Normal alleles contain 25 to 40 CAG/CAA repeats, alleles with 50 or greater CAG/CAA repeats are pathological with full penetrance. Alleles with 43 to 49 CAG/CAA repeats were also reported and their penetrance is estimated between 50 and 80%. Recently few symptomatic individuals having 41 and 42 repeats were reported but it is still unclear whether CAG/CAA repeats of 41 or 42 are low penetrance disease-causing alleles. Thus, phenotypic variability like the disease course in subject with SCA17 locus restricted expansions remains to be fully understood. CASE PRESENTATION: The patients was a 63-year-old woman who, at 54 years, showed personality changes and increased frequency of falls. At 55 years of age neuropsychological tests showed executive attention and visuospatial deficit. At the age of 59 the patient developed dysarthria and a progressive cognitive deficit. The neurological examination showed moderate gait ataxia, dysdiadochokinesia and dysmetria, dysphagia, dysarthria and abnormal saccadic pursuit, severe axial asynergy during postural changes, choreiform dyskinesias. Molecular analysis of the TBP gene demonstrated an allele with 41 repeat suggesting that 41 CAG/CCG TBP repeats could be an allele associated with the full clinical spectrum of SCA17. CONCLUSIONS: The described case with the other similar cases described in the literature suggests that 41 CAG/CAA trinucleotides should be considered as critical threshold in SCA17. We suggest that SCA17 diagnosis should be suspected in patients presenting with movement disorders associated with other neurodegenerative signs and symptoms.
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spelling pubmed-58529642018-03-21 Spinocerebellar ataxia 17: full phenotype in a 41 CAG/CAA repeats carrier Origone, Paola Gotta, Fabio Lamp, Merit Trevisan, Lucia Geroldi, Alessandro Massucco, Davide Grazzini, Matteo Massa, Federico Ticconi, Flavia Bauckneht, Matteo Marchese, Roberta Abbruzzese, Giovanni Bellone, Emilia Mandich, Paola Cerebellum Ataxias Case Report BACKGROUND: Spinocerebellar ataxia 17 (SCA17) is one of the most heterogeneous forms of autosomal dominant cerebellar ataxias with a large clinical spectrum which can mimic other movement disorders such as Huntington disease (HD), dystonia and parkinsonism. SCA17 is caused by an expansion of CAG/CAA repeat in the Tata binding protein (TBP) gene. Normal alleles contain 25 to 40 CAG/CAA repeats, alleles with 50 or greater CAG/CAA repeats are pathological with full penetrance. Alleles with 43 to 49 CAG/CAA repeats were also reported and their penetrance is estimated between 50 and 80%. Recently few symptomatic individuals having 41 and 42 repeats were reported but it is still unclear whether CAG/CAA repeats of 41 or 42 are low penetrance disease-causing alleles. Thus, phenotypic variability like the disease course in subject with SCA17 locus restricted expansions remains to be fully understood. CASE PRESENTATION: The patients was a 63-year-old woman who, at 54 years, showed personality changes and increased frequency of falls. At 55 years of age neuropsychological tests showed executive attention and visuospatial deficit. At the age of 59 the patient developed dysarthria and a progressive cognitive deficit. The neurological examination showed moderate gait ataxia, dysdiadochokinesia and dysmetria, dysphagia, dysarthria and abnormal saccadic pursuit, severe axial asynergy during postural changes, choreiform dyskinesias. Molecular analysis of the TBP gene demonstrated an allele with 41 repeat suggesting that 41 CAG/CCG TBP repeats could be an allele associated with the full clinical spectrum of SCA17. CONCLUSIONS: The described case with the other similar cases described in the literature suggests that 41 CAG/CAA trinucleotides should be considered as critical threshold in SCA17. We suggest that SCA17 diagnosis should be suspected in patients presenting with movement disorders associated with other neurodegenerative signs and symptoms. BioMed Central 2018-03-14 /pmc/articles/PMC5852964/ /pubmed/29564144 http://dx.doi.org/10.1186/s40673-018-0086-x Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Case Report
Origone, Paola
Gotta, Fabio
Lamp, Merit
Trevisan, Lucia
Geroldi, Alessandro
Massucco, Davide
Grazzini, Matteo
Massa, Federico
Ticconi, Flavia
Bauckneht, Matteo
Marchese, Roberta
Abbruzzese, Giovanni
Bellone, Emilia
Mandich, Paola
Spinocerebellar ataxia 17: full phenotype in a 41 CAG/CAA repeats carrier
title Spinocerebellar ataxia 17: full phenotype in a 41 CAG/CAA repeats carrier
title_full Spinocerebellar ataxia 17: full phenotype in a 41 CAG/CAA repeats carrier
title_fullStr Spinocerebellar ataxia 17: full phenotype in a 41 CAG/CAA repeats carrier
title_full_unstemmed Spinocerebellar ataxia 17: full phenotype in a 41 CAG/CAA repeats carrier
title_short Spinocerebellar ataxia 17: full phenotype in a 41 CAG/CAA repeats carrier
title_sort spinocerebellar ataxia 17: full phenotype in a 41 cag/caa repeats carrier
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852964/
https://www.ncbi.nlm.nih.gov/pubmed/29564144
http://dx.doi.org/10.1186/s40673-018-0086-x
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