High frequency of multiexonic deletion of the GCH1 gene in a Taiwanese cohort of dopa-response dystonia

Yah Huei Wu-Chou, Tu Hsueh Yeh, Chuan Yu Wang, Juei Jueng Lin, Chin Chang Huang, Hsiu Chen Chang, Szu Chia Lai, Rou Shayn Chen, Yi Hsin Weng, Chia Ling Huang, Chin Song Lu

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17 Citations (Scopus)


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); Ser81-Pro (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-timePCRanalysis. 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 fromthose in Parkinson's disease. In conclusion, a high frequency of multi-exonic 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.

Original languageEnglish
Pages (from-to)903-908
Number of pages6
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Issue number4
Publication statusPublished - Jun 2010


  • GCH1 deletion
  • MLPA
  • qPCR
  • Segawa's disease

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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