The frequency of spinocerebellar ataxia type 23 in a UK population

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• 作者：Katherine Fawcett (1)
  Mohadeseh Mehrabian (2)
  Yo-Tsen Liu (1) (3) (4)
  Sherifa Hamed (5)
  Elahe Elahi (6)
  Tamas Revesz (1)
  Georgios Koutsis (7)
  Joshua Herscheson (1)
  Lucia Schottlaender (1)
  Mark Wardle (8)
  Patrick J. Morrison (9)
  Huw R. Morris (8)
  Paola Giunti (1)
  Nicholas Wood (1)
  Henry Houlden (1)
  
• 关键词：Spinocerebellar ataxia 23 ; Preproenkephalin ; Genetics ; Mutation
• 刊名：Journal of Neurology
• 出版年：2013
• 出版时间：March 2013
• 年：2013
• 卷：260
• 期：3
• 页码：856-859
• 全文大小：163KB
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  9. Kobayashi H, Abe K, Matsuura T, Ikeda Y, Hitomi T, Akechi Y, Habu T, Liu W, Okuda H, Koizumi A (2011) Expansion of intronic GGCCTG hexanucleotide repeat in NOP56 causes SCA36, a type of spinocerebellar ataxia accompanied by motor neuron involvement. Am J Hum Genet. doi:10.1016/j.ajhg.2011.05.015
  10. Schicks J, Synofzik M, Beetz C, Schiele F, Schols L (2011) Mutations in the PDYN gene (SCA23) are not a frequent cause of dominant ataxia in Central Europe. Clin Genet 80(5):503-04. doi:10.1111/j.1399-0004.2011.01651.x CrossRef
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• 作者单位：Katherine Fawcett (1)
  Mohadeseh Mehrabian (2)
  Yo-Tsen Liu (1) (3) (4)
  Sherifa Hamed (5)
  Elahe Elahi (6)
  Tamas Revesz (1)
  Georgios Koutsis (7)
  Joshua Herscheson (1)
  Lucia Schottlaender (1)
  Mark Wardle (8)
  Patrick J. Morrison (9)
  Huw R. Morris (8)
  Paola Giunti (1)
  Nicholas Wood (1)
  Henry Houlden (1)
  
  1. Department of Molecular Neuroscience, Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London, WC1N 3BG, UK
  2. Tanz Centre for Research in Neurodegenerative Diseases and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
  3. Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan
  4. National Yang-Ming University School of Medicine, Taipei, Taiwan
  5. School of Biology and Department of Biotechnology, University College of Science, University of Tehran, Tehran, Iran
  6. Department of Neurology, Cairo University, Giza, Egypt
  7. Neurogenetics Unit, Department of Neurology, University of Athens Medical School, Eginitio Hospital, Athens, Greece
  8. MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK
  9. School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, Northern Ireland, UK
  
• ISSN：1432-1459

文摘

Spinocerebellar ataxias (SCA) are a genetically heterogeneous group of neurodegenerative diseases characterised by progressive cerebellar ataxia, dysarthria and oculomotor abnormalities. Recently the prodynorphin (PDYN) gene was identified as the cause of SCA23 in four Dutch families displaying progressive gait and limb ataxia. In this study we aimed to assess the frequency of PDYN gene defects and extend the phenotype of SCA23 patients in a UK ataxia series and also in patients from Greece, Egypt and India. We sequenced the coding and flanking intronic regions of the PDYN gene in a total of 852 ataxia patients, of which 356 were sporadic with no family history, 320 had a positive family history, and 176 probands had a positive family history and at least one family member had also been investigated. We also analysed 190 patients with multiple-system atrophy with cerebellar features (MSA-C), a phenocopy of SCA23. We identified a novel putative pathogenic heterozygous missense variant in the PDYN gene in an early onset SCA patient with an unknown family history. This variant was not present in 570 matched British controls. This is the first study to screen for SCA23 in UK patients and confirms that PDYN mutations are a very rare cause of spinocerebellar ataxia, accounting for?~?0.1?% of ataxia cases but perhaps with a higher frequency in pure cerebellar ataxia. Given the rarity of PDYN mutations, front-line diagnostic evaluation of UK familial and early onset pure spinocerebellar ataxia patients should focus on other known ataxia genes.