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Journal of Neural Transmission

, Volume 119, Issue 11, pp 1343–1350 | Cite as

Occurrence of GCH1 gene mutations in a group of Indian dystonia patients

  • Tufan Naiya
  • Amar K. Misra
  • Arindam Biswas
  • Shyamal K. Das
  • Kunal Ray
  • Jharna Ray
Basic Neurosciences, Genetics and Immunology - Original Article

Abstract

The aim of this study is to examine the role of GCH1 among Indians affected with dopa responsive dystonia (DRD) and early onset Parkinson’s disease (EOPD). The patients (n = 76 including 19 DRD and 36 EOPD) and controls (n = 138) were screened for variants in GCH1 by PCR amplification of exons, splice junctions and 1 kb upstream region followed by SSCP and DNA sequencing. Four novel variants (p.Met1Val, p.Val204_205del, IVS3+68A>G, and IVS5−6T>G) were identified in 10 patients but not in the controls. In addition to two nonsynonymous changes, identified in four DRD patients in heterozygous condition, one intronic variant (IVS5−6T>G) could be linked to pathogenesis of the disease since it has the potential of altering the splice site as assessed by in silico analysis. Patients carrying different nonsynonymous variants had remarkable variation in clinical phenotype. Consistent with earlier reports, severity of clinical phenotype and the age of onset varied among family members harboring the same mutation. No mutation was detected in the EOPD patients. Three novel mutations in GCH1 gene have been found and are shown to be associated with variable clinical phenotypes mostly within the spectrum of DRD. The mutations identified represent 15.79% (3/19) of east Indian DRD patient cohort.

Keywords

Dopa responsive dystonia (DRD) Dystonia EOPD GCH1 

Notes

Acknowledgments

The authors are thankful to the patients for participating in the study. The study was supported partially by grants from University Grant Commission [Grant no. F.14-38/2007(Inno./ASIST)] and Council of Scientific and Industrial Research (CSIR) (Grant no. MLP-0016 and SIP-007). TN is supported by a fellowship from CSIR, India. AB is supported by a fellowship from ICMR, India.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Tufan Naiya
    • 1
  • Amar K. Misra
    • 2
  • Arindam Biswas
    • 1
  • Shyamal K. Das
    • 2
  • Kunal Ray
    • 3
  • Jharna Ray
    • 1
  1. 1.S. N. Pradhan Centre for NeurosciencesUniversity of CalcuttaKolkataIndia
  2. 2.Bangur Institute of NeurosciencesKolkataIndia
  3. 3.Molecular & Human Genetics DivisionCSIR-Indian Institute of Chemical BiologyKolkataIndia

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