Mutations in the cyclic adenosine monophosphate response element of the tyrosine hydroxylase gene

Abstract Tyrosine hydroxylase (TH) deficiency (OMIM 191290) is one cause of early‐onset dopa‐responsive dystonia. We describe seven cases from five unrelated families with dopa‐responsive dystonia and low homovanillic acid in cerebrospinal fluid who were suspected to suffer from TH deficiency. Analysis of part of the TH promotor showed five homozygous and two heterozygous mutations in the highly conserved cyclic adenosine monophosphate response element. Our data suggest that, if no mutations are found in the coding regions of the gene in patients strongly suspected of TH deficiency, the search for pathogenic mutations should be extended to regulatory promotor elements. Ann Neurol 2007