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

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.

Figure 1. Pedigree of a Colombian Family with DYT-5 dystonia. Only women affected. Genetic analysis in the index case (arrow) revealed a new mutation in exon 1.

Figure 2. GCH1 Mutation. Upper panel, wild-type sequence from unaffected control. Lower panel, deletion of G nucleotide, signified by red arrowhead, (c.159delG, based on sequence accession number NM_000161), which results in a frame shift and the creation of a premature stop codon p.W53X (based on sequences accession number NP_000152.1).