Mutations in the gene encoding ɛ-sarcoglycan cause myoclonus–dystonia syndrome
The dystonias are a common clinically and genetically heterogeneous group of movement disorders. More than ten loci for inherited forms of dystonia have been mapped, but only three mutated genes have been identified so far. These are DYT1 , encoding torsin A 1 and mutant in the early-onset generaliz...
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Veröffentlicht in: | Nature genetics 2001-08, Vol.29 (1), p.66-69 |
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Zusammenfassung: | The dystonias are a common clinically and genetically heterogeneous group of movement disorders. More than ten loci for inherited forms of dystonia have been mapped, but only three mutated genes have been identified so far. These are
DYT1
, encoding torsin A
1
and mutant in the early-onset generalized form,
GCH1
(formerly known as
DYT5
), encoding GTP–cyclohydrolase I and mutant in dominant dopa-responsive dystonia
2
, and
TH
, encoding tyrosine hydroxylase and mutant in the recessive form of the disease
3
. Myoclonus–dystonia syndrome (MDS;
DYT11
) is an autosomal dominant disorder characterized by bilateral, alcohol-sensitive myoclonic jerks involving mainly the arms and axial muscles
4
,
5
. Dystonia, usually torticollis and/or writer's cramp, occurs in most but not all affected patients and may occasionally be the only symptom of the disease
6
,
7
. In addition, patients often show prominent psychiatric abnormalities, including panic attacks and obsessive–compulsive behavior
8
,
9
,
10
. In most MDS families, the disease is linked to a locus on chromosome 7q21 (refs.
11
–
13
). Using a positional cloning approach, we have identified five different heterozygous loss-of-function mutations in the gene for ɛ-sarcoglycan (
SGCE
), which we mapped to a refined critical region of about 3.2 Mb.
SGCE
is expressed in all brain regions examined. Pedigree analysis shows a marked difference in penetrance depending on the parental origin of the disease allele. This is indicative of a maternal imprinting mechanism, which has been demonstrated in the mouse ɛ-sarcoglycan gene
14
. |
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ISSN: | 1061-4036 1546-1718 |
DOI: | 10.1038/ng709 |