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Heterogeneity in clinical features and disease severity in ataxia-associated SYNE1 mutations.
Wiethoff, Sarah; Hersheson, Joshua; Bettencourt, Conceicao; Wood, Nicholas W; Houlden, Henry.
Afiliação
  • Wiethoff S; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
  • Hersheson J; Centre for Neurology and Hertie Institute for Clinical Brain Research, Eberhard-Karls-University, Tübingen, Germany.
  • Bettencourt C; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
  • Wood NW; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
  • Houlden H; Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
J Neurol ; 263(8): 1503-10, 2016 Aug.
Article em En | MEDLINE | ID: mdl-27178001
The autosomal recessive spinocerebellar ataxias are an exciting field of study, with a growing number of causal genes and an expanding phenotypic spectrum. SYNE1 was originally discovered in 2007 as the causal gene underlying autosomal recessive spinocerebellar ataxia 1, a disease clinically thought to manifest with mainly pure cerebellar ataxia. Since the original report SYNE1 mutations have also been identified in families with motor neuronopathy and arthrogryposis but few families have been screened as the gene is very large at 146 exons in length. We screened 196 recessive and sporadic ataxia patients for mutations in SYNE1 using next generation sequencing in order to assess its frequency and extend the clinicogenetic spectrum. We identified four novel truncating mutations spread throughout the SYNE1 gene from three families living in London that originated from England, Turkey and Sri Lanka. The phenotype was mainly pure cerebellar ataxia in two families, cognitive decline was present in all three families, axonal neuropathy in one family and marked spasticity in the Turkish family, with a range of disease severities. Searching for genotype-phenotype correlations in the SYNE1 gene, defects located near the 3' prime end of the gene are more frequently associated with motor neuron or neuromuscular involvement so far. Our data indicate SYNE1 mutations are not an uncommon cause of recessive ataxia with or without additional clinical features in patients from various ethnicities. The use of next generation sequencing allows the rapid analysis of large genes and will likely reveal more SYNE1 associated cases and further expand genotype-phenotype correlations.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linhagem / Proteínas Nucleares / Ataxia Cerebelar / Mutação / Proteínas do Tecido Nervoso Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male País/Região como assunto: Asia / Europa Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linhagem / Proteínas Nucleares / Ataxia Cerebelar / Mutação / Proteínas do Tecido Nervoso Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male País/Região como assunto: Asia / Europa Idioma: En Ano de publicação: 2016 Tipo de documento: Article