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.
Ribasés
Marta
M
Departament de Psiquiatria, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Serrano
Mercedes
M
Fernández-Alvarez
Emilio
E
Pahisa
Sandra
S
Ormazabal
Aida
A
García-Cazorla
Angels
A
Pérez-Dueñas
Belén
B
Campistol
Jaume
J
Artuch
Rafael
R
Cormand
Bru
B
D001925:Brain Damage, Chronic / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D000242:Cyclic AMP / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000627:therapeutic use*; D015259:Dopamine Agents / Q000627:therapeutic use*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006720:Homozygote; D006801:Humans; D017354:Point Mutation / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020218:Response Elements / Q000235:genetics*; D014158:Transcription, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D015259:Dopamine Agents; D004295:Dihydroxyphenylalanine; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase