A Novel DYT-5 Mutation with Phenotypic Variability within a Colombian Family

Tremor Other Hyperkinet Mov (N Y). 2013 Oct 10:3:tre-03-138-4462-2. doi: 10.7916/D86W98SW. eCollection 2013.

Abstract

Background: DYT-5 dystonia usually presents as a dopa-responsive dystonia (DRD) with early or late parkinsonian manifestations and/or dystonic features. Genetically, these patients have been described as having a wide array of independent mutations in the guanosine triphosphate cyclohydrolase 1 gene (GCH1), and these patients may also have a wide array of clinical manifestations.

Methods: A Colombian family with six affected female members was characterized.

Results: Three members, including the index case, revealed mild parkinsonism, whereas three granddaughters of the index case showed severe generalized dystonia. No men were affected. There was anticipation, and a female predominance was uncovered. Treatment with levodopa was generally effective except in a case with severe skeletal deformities and contractions. Detailed genetic analysis in the index case revealed a new mutation in exon 1 of GCH1 (c.159delG).

Discussion: This study revealed a new mutation of GCH1 that resulted in heterogeneous clinical presentations of DRD within a large family.

Keywords: DRD, dopamine; Parkinson's disease; dystonia, genetics.