A rare novel deletion of the tyrosine hydroxylase gene in Parkinson disease

Güney Bademci, Todd L. Edwards, Andre L. Torres, William K Scott, Stephan L Zuchner, Eden R Martin, Jeffery M Vance, Liyong Wang

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Tyrosine hydroxylase (TH) enzyme is a rate limiting enzyme in dopamine biosynthesis. Missense mutation in both alleles of the TH gene is known to cause dopamine-related phenotypes, including dystonia and infantile Parkinsonism. However, it is not clear if single allele mutation in TH modifies the susceptibility to the adult form of Parkinson disease (PD). We reported a novel deletion of entire TH gene in an adult with PD. The deletion was first identified by copy number variation (CNV) analysis in a genome-wide association study using Illumina Infinium BeadChips. After screening 635 cases and 642 controls, the deletion was found in one PD case but not in any control. The deletion was confirmed by multiple quantitative PCR (qPCR) assays. There is no additional exonic single nucleotide variant in the one copy of TH gene of the patient. The patient has an age-at-onset of 54 years, no evidence for dystonia, and was responsive to L-DOPA. This case supports the importance of the TH gene in PD pathogenesis and raises more attention to rare variants in candidate genes being a risk factor for Parkinson disease.

Original languageEnglish
JournalHuman Mutation
Volume31
Issue number10
DOIs
StatePublished - Oct 1 2010

Fingerprint

Tyrosine 3-Monooxygenase
Parkinson Disease
Genes
Dopamine
Alleles
Dystonia
Genome-Wide Association Study
Missense Mutation
Enzymes
Age of Onset
Nucleotides
Phenotype
Polymerase Chain Reaction
Mutation

Keywords

  • CNV
  • Deletion
  • Parkinson disease
  • Rare variants
  • TH

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

A rare novel deletion of the tyrosine hydroxylase gene in Parkinson disease. / Bademci, Güney; Edwards, Todd L.; Torres, Andre L.; Scott, William K; Zuchner, Stephan L; Martin, Eden R; Vance, Jeffery M; Wang, Liyong.

In: Human Mutation, Vol. 31, No. 10, 01.10.2010.

Research output: Contribution to journalArticle

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