Heterozygous mutation in 5'-untranslated region of sepiapterin reductase gene (SPR) in a patient with dopa-responsive dystonia.

The search for mutations in genes coding for components of the biopterin pathway other than GTPCH1 revealed a mutation in the gene coding for sepiapterin reductase (SPR) in 1 of 95 patients with GCH1-negative dopa-responsive dystonia (DRD). The mutation detected in SPR is a G-->A transition at position -13 of the untranslated region of the gene. This resulted in drastically reduced activity of sepiapterin reductase in the patient's fibroblasts. The findings indicate that haploinsufficiency of SPR can be a rare cause of DRD.