GCH1 molecular analysis in dopa responsive dystonia

Abstract

Dopa responsive dystonia (DRD) linked to the DYT5 locus is an autosomal dominant inherited disorder caused by mutations in the GCH1 gene. It is characterized by onset during childhood, with gate disorder due to dystonia plus parkinsonian symptoms, with excellent response to levodopa. Not infrequently DRD is misdiagnosed as cerebral palsy, delaying the treatment, which can lead to important motor sequelae. Several mutations have been described in GCH1, but such studies are rare in Brazil. Molecular diagnosis can help to clarify those cases where clinical features are not so clear. In this work, we aim to establish molecular techniques to investigate GCH1 mutations in DDR patients. Patients from both genders with clinical diagnoses of DDR will have their genomic DNA extracted from peripheral blood. Mutations will be investigated with direct sequencing and gene dosage with real-time PCR. Results will be compared with those in the literature and correlated to the clinical phenotype. (AU)