A homozygous frameshift mutation of sepiapterin reductase gene causing parkinsonism with onset in childhood

Parkinsonism Relat Disord. 2012 Feb;18(2):191-3. doi: 10.1016/j.parkreldis.2011.10.001. Epub 2011 Oct 21.


We report two siblings that presented hypotonia and very early-onset parkinsonism. Homozygosity mapping using SNP genome scan data identified a candidate locus that was 12.2 Mega base pairs. By exome sequencing, we found a homozygous five-nucleotide deletion (c.448_452delAGAAC) in gene Sepiapterin Reductase (SPR). The mutation is predicted to lead to premature translational termination. Sepiapterin reductase deficiency (SRD) is a recently recognized dopa-responsive dystonia. Our findings show that SRD can manifest as early-onset parkinsonism, widening the spectrum of the disease phenotype and adding to the genetic heterogeneity of the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Alcohol Oxidoreductases / genetics*
  • Child
  • Female
  • Frameshift Mutation*
  • Gene Deletion*
  • Homozygote*
  • Humans
  • Male
  • Middle Aged
  • Parkinsonian Disorders / diagnosis
  • Parkinsonian Disorders / genetics*


  • Alcohol Oxidoreductases
  • sepiapterin reductase