Assessing the role of DRD5 and DYT1 in two different case–control series with primary blepharospasm

Abstract

Primary blepharospasm is a common adult-onset focal dystonia. Polymorphisms of the genes encoding TorsinA (DYT1) and the D5 dopamine receptor (DRD5) have previously been associated with lifetime risk for focal dystonia. We describe here experiments testing common variability within these two genes in two independent cohorts of Italian and North American patients with primary blepharospasm. We have failed to identify a consistent association with disease in the two patient groups examined here; however, analysis of the Italian group reveals an association with the same risk genotype in DYT1 as previously described in an Icelandic population. We have also found global significant DYT1 haplotype differences between patients and controls in the Italian series. These data suggest that further examination is warranted of the role genetic variability at this locus plays in the risk for primary dystonia.

Genetics of Primary Torsion Dystonia

“…In another study, this SNP failed to show a difference in genotype distribution between adult-onset cranial-cervical dystonia patients and controls from an Italian cohort [27]. Contradictory findings also were reported for a microsatellite polymorphism in the gene for the dopamine D5 receptor (DRD5), with a twofold increased risk for dystonia in Italian cervical dystonia patients carrying a specific allele [28] but not in independent cohorts of Italian and North American patients with primary blepharospasm [29] and German patients with various forms of primary dystonia [30]. Numerous studies explored the influence of polymorphisms in the DYT1 gene.…”

Association of rs1182 polymorphism of the DYT1 gene with primary dystonia in Chinese population

“…However, the finding was replicated neither in American cohort [16] nor in a second German cohort [19]. The ethnicity factor is known to have important implications in genetic analyses.…”

“…Recently, the single nucleotide polymorphism (SNP) rs1182 (191 G/T) at 3′-untranslated region (3′-UTR) in the DYT1 gene has been linked to increased risk for primary dystonia in Italian [16], Icelandic [17], German and Austrian cohorts [18]. However, the finding was replicated neither in American cohort [16] nor in a second German cohort [19].…”

Inherited Isolated Dystonia: Clinical Genetics and Gene Function

“…No studies have identified genetic or environmental factors that contribute to the striking variability in disease severity among manifesting subjects. Studies examining a possible association of torsinA sequence variation with adult-onset idiopathic isolated dystonia are mixed [22][23][24][25][26]. No evidence has been found linking TOR1A to susceptibility to causes of dystonia such as neuroleptic drugs or perinatal asphyxia [27].…”