High frequency of multiexonic deletion of the GCH1 gene in a Taiwanese cohort of dopa-response dystonia.
Am J Med Genet B Neuropsychiatr Genet
; 153B(4): 903-8, 2010 Jun 05.
Article
in En
| MEDLINE
| ID: mdl-20082337
ABSTRACT
Large deletions in the GCH1 gene have been reported in a minority of cases of dopa-responsive dystonia (DRD). In this study, we performed an extensive clinical and genetic investigation of 22 affected members in eight families. Sequence analysis revealed five different mutations in five families (n = 10); Ser81Pro (novel), Ser76X, Gly203Arg, 249del A, and IVS5 + 3insT. Applying multiple ligation-dependent probe amplification analysis, we detected a large heterozygous deletion of exons 1-3 in the remaining three families (n = 12), which was verified by quantitative real-time PCR analysis. Therefore, the large deletion accounted for 37.5% of the total families and 55% of our DRD population. The deletion appeared to have high penetrance and was associated with multifocal dystonia and adult onset in males. Adult-onset patients were commonly presenting with resting tremor, rigidity, and bradykinesia, indistinguishable from those in Parkinson's disease. In conclusion, a high frequency of multiexonic deletion of GCH1 was identified in the Taiwanese DRD population. By dosage analysis, we were able to detect a mutation in all patients. Our study demonstrates that dosage analysis is necessary for molecular diagnostics in DRD patients of Han Chinese ethnicity.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Dihydroxyphenylalanine
/
Sequence Deletion
/
Dystonic Disorders
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Asian People
/
Dystonia
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
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Female
/
Humans
/
Male
Language:
En
Journal:
Am J Med Genet B Neuropsychiatr Genet
Journal subject:
GENETICA MEDICA
/
NEUROLOGIA
/
PSIQUIATRIA
Year:
2010
Document type:
Article
Affiliation country:
Taiwan