期刊
JOURNAL OF NEUROLOGY
卷 261, 期 12, 页码 2296-2304出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00415-014-7488-3
关键词
Myoclonus; Dystonia; Genetic and inherited disorders; SGCE
资金
- Ipsen Clinical Research Fellowship
- Welsh Clinical Academic Track (WCAT) program
- GOSHCC
- Wellcome Trust
- Medical Research Council
- Action Medical Research, The Dystonia Society UK
- Guy's and St Thomas' Charity
- Parkinson's UK
- East Kent
- King's College Hospital Foundation Trusts
- Children's fund for health at The Children's University Hospital, Temple Street, Dublin
- Brain Research Trust
- Cure Huntington's Disease Initiative
- Dystonia Society
- Bachmann-Strauss Dystonia Parkinson Foundation
- NHS Innovations Ltd
- Academy of Medical Sciences (AMS) [AMS-SGCL11-Peall] Funding Source: researchfish
- Medical Research Council [G1100643, G0801418, MR/K000608/1, G0700943, MR/L010305/1] Funding Source: researchfish
- MRC [G0700943, G0801418, G1100643, MR/K000608/1] Funding Source: UKRI
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 a parts per thousand currency sign10 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.
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