Myoclonus-dystonia: clinical and genetic evaluation of a large cohort.
BACKGROUND
Myoclonus-dystonia (M-D) is an autosomal dominant inherited movement disorder. Various mutations within the epsilon-sarcoglycan (SGCE) gene have been associated with M-D, but mutations are detected in only about 30% of patients. The lack of stringent clinical inclusion criteria and limitations of mutation screens by direct sequencing might explain this observation.


METHODS
Eighty-six M-D index patients from the Dutch national referral centre for M-D underwent neurological examination and were classified according to previously published criteria into definite, probable and possible M-D. Sequence analysis of the SGCE gene and screening for copy number variations were performed. In addition, screening was carried out for the 3 bp deletion in exon 5 of the DYT1 gene.


RESULTS
Based on clinical examination, 24 definite, 23 probable and 39 possible M-D patients were detected. Thirteen of the 86 M-D index patients carried a SGCE mutation: seven nonsense mutations, two splice site mutations, three missense mutations (two within one patient) and one multiexonic deletion. In the definite M-D group, 50% carried an SGCE mutation and one single patient in the probable group (4%). One possible M-D patient showed a 4 bp deletion in the DYT1 gene (c.934_937delAGAG).


CONCLUSIONS
Mutation carriers were mainly identified in the definite M-D group. However, in half of definite M-D cases, no mutation could be identified. Copy-number variations did not play a major role in the large cohort.
Ritz
K
K
Department of Neurology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Gerrits
M C F
MC
Foncke
E M J
EM
van Ruissen
F
F
van der Linden
C
C
Vergouwen
M D I
MD
Bloem
B R
BR
Vandenberghe
W
W
Crols
R
R
Speelman
J D
JD
Baas
F
F
Tijssen
M A J
MA
D000293:Adolescent; D000328:Adult; D020029:Base Pairing / Q000235:genetics; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D015331:Cohort Studies; D004421:Dystonia / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D005799:Genes, Dominant / Q000235:genetics*; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D009207:Myoclonus / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D009460:Neurologic Examination; D049031:Sarcoglycans / Q000235:genetics*; D017422:Sequence Analysis, DNA; D055815:Young Adult
D018832:Molecular Chaperones; C526572:SGCE protein, human; D049031:Sarcoglycans; C108175:TOR1A protein, human