SGCE and myoclonus dystonia: motor characteristics, diagnostic criteria and clinical predictors of genotype

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• 作者：Kathryn J. Peall (1)
  Manju A. Kurian (2) (3)
  Mark Wardle (1)
  Adrian J. Waite (1)
  Tammy Hedderly (4)
  Jean-Pierre Lin (4)
  Martin Smith (5)
  Alan Whone (6)
  Hardev Pall (7)
  Cathy White (8)
  Andrew Lux (9)
  Philip E. Jardine (9)
  Bryan Lynch (10)
  George Kirov (1)
  Sean O’Riordan (11)
  Michael Samuel (12)
  Timothy Lynch (13)
  Mary D. King (10)
  Patrick F. Chinnery (14)
  Thomas T. Warner (15)
  Derek J. Blake (1)
  Michael J. Owen (1)
  Huw R. Morris (15)
  
• 关键词：Myoclonus ; Dystonia ; Genetic and inherited disorders ; SGCE
• 刊名：Journal of Neurology
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：261
• 期：12
• 页码：2296-2304
• 全文大小：463 KB
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  13. Grabowski M et al (2003) The epsilon-sarcoglycan gene ( / SGCE), mutated in myoclonus-dystonia syndrome, is maternally imprinted. Eur J Hum Genet 11(2):138-44 j.ejhg.5200938" target="_blank" title="It opens in new window">CrossRef
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• 作者单位：Kathryn J. Peall (1)
  Manju A. Kurian (2) (3)
  Mark Wardle (1)
  Adrian J. Waite (1)
  Tammy Hedderly (4)
  Jean-Pierre Lin (4)
  Martin Smith (5)
  Alan Whone (6)
  Hardev Pall (7)
  Cathy White (8)
  Andrew Lux (9)
  Philip E. Jardine (9)
  Bryan Lynch (10)
  George Kirov (1)
  Sean O’Riordan (11)
  Michael Samuel (12)
  Timothy Lynch (13)
  Mary D. King (10)
  Patrick F. Chinnery (14)
  Thomas T. Warner (15)
  Derek J. Blake (1)
  Michael J. Owen (1)
  Huw R. Morris (15)
  
  1. MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK
  2. Neurogenetics Unit, Developmental Neurosciences, UCL-Institute of Child Health, London, UK
  3. Department of Neurology, Great Ormond Street Hospital, London, UK
  4. Evelina Children’s Hospital, St Thomas-Hospital, London, UK
  5. Birmingham Children’s Hospital, Birmingham, UK
  6. Department of Neurology, Frenchay Hospital, Bristol, UK
  7. School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK
  8. Department of Paediatrics, Singleton Hospital, Swansea, UK
  9. Bristol Royal Hospital for Children, Bristol, UK
  10. Children’s University Hospital, Temple Street, Dublin, Ireland
  11. St. Vincent’s University Hospital, Dublin, Ireland
  12. Department of Neurology, East Kent Hospitals NHS Foundation Trust, Ashford, Kent.and King’s College Hospital, King’s Health Partners, London, UK
  13. Mater Misericordiae University Hospital, Dublin, Ireland
  14. Institute of Genetic Medicine, Newcastle University, Newcastle, UK
  15. Department of Clinical Neurosciences, UCL Institute of Neurology, London, UK
  
• ISSN：1432-1459

文摘

Myoclonus dystonia syndrome (MDS) is a young-onset movement disorder. A proportion of cases are due to mutations in the maternally imprinted SGCE gene. We assembled the largest cohort of MDS patients to date, and determined the frequency and type of SGCE mutations. The aim was to establish the motor phenotype in mutation carriers and utility of current diagnostic criteria. Eighty-nine probands with clinical features compatible with MDS were recruited from the UK and Ireland. Patients were phenotypically classified as “definite- “probable-or “possible-MDS according to previous guidelines. SGCE was analyzed using direct sequencing and copy number variant analysis. In those where no mutation was found, DYT1 (GAG deletion), GCH1, THAP1 and NKX2.1 genes were also sequenced. Nineteen (21.3?%) probands had an SGCE mutation. Three patterns of motor symptoms emerged: (1) early childhood onset upper body myoclonus and dystonia, (2) early childhood onset lower limb dystonia, progressing later to more pronounced myoclonus and upper body involvement, and (3) later childhood onset upper body myoclonus and dystonia with evident cervical involvement. Five probands had large contiguous gene deletions ranging from 0.7 to 2.3?Mb in size with distinctive clinical features, including short stature, joint laxity and microcephaly. Our data confirms that SGCE mutations are most commonly identified in MDS patients with (1) age at onset ?0?years and (2) predominant upper body involvement of a pure myoclonus-dystonia. Cases with whole SGCE gene deletions had additional clinical characteristics, which are not always predicted by deletion size or gene involvement.