A homozygous tyrosine hydroxylase gene promoter mutation in a patient with dopa-responsive encephalopathy: Clinical, biochemical and genetic analysis

We report a recessive mutation in the tyrosine hydroxylase gene (TH) promoter (c.1−71C>T), present at homozygosity in a patient with dopa-responsive encephalopathy. The change lies in a cAMP response element (CRE) and alters a binding site for the CREM transcription factor. Previous studies support that the CRE in the TH gene is essential for its transcription, suggesting that mutations within this consensus motif may cause an impairment of catecholamine biosynthesis and lead to a pathogenic phenotype.