A novel locus for inherited myoclonus-dystonia on 18p11.
OBJECTIVE
Inherited myoclonus-dystonia (IMD) is a new term for an autosomal dominant disorder characterized by myoclonus and dystonia. Recently, IMD was linked to a region on chromosome 11q23 with two different mutations identified in the D2 dopamine receptor gene and linked to chromosome 7q with five different loss-of-function mutations identified in the epsilon-sarcoglycan gene.


METHODS
These two regions and genes were excluded in a large Canadian family with IMD in whom 13 individuals are affected. A 25-cM genome scan of this large family with 32 individuals was performed.


RESULTS
Two-point linkage analysis revealed a maximum lod score of 3.5 (recombination fraction 0.00; affected only) for the microsatellite marker GATA185C06-18 and a multipoint lod score of 3.9 across the 18p11 region. Haplotype analysis demonstrates that all the affected individuals shared a common haplotype between markers D18S1132 and D18S843 that defines the disease gene within a span of 16.9 cM.


CONCLUSIONS
These findings indicate that a novel IMD gene exists on chromosome 18p11.
Grimes
D A
DA
Department of Medicine, Division of Neurology, The Ottawa Hospital, Ottawa, Canada. dagrimes@ottawahospital.on.ca
Han
F
F
Lang
A E
AE
St  George-Hyssop
P
P
Racacho
L
L
Bulman
D E
DE
D002648:Child; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D004421:Dystonia / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009207:Myoclonus / Q000235:genetics*; D010375:Pedigree; D017448:Receptors, Dopamine D2 / Q000235:genetics; D013577:Syndrome
D017448:Receptors, Dopamine D2