THAP1 mutations in a Greek primary blepharospasm series.

1353-8020/$ – see front matter 2012 Elsevier Ltd. http://dx.doi.org/10.1016/j.parkreldis.2012.08.015 Benign essential blepharospasm (BEB) is an adult onset focal dystonia that manifests as forced involuntary eyelid closure usually starting between the fifth and the seventh decade [1]. The frequency is rare; affecting around 1 in 20,000 people, where most of the cases are sporadic, approximately 20–30% of patients may have a positive family history, thus indicating a possible genetic contribution in the aetiology of blepharospasm [1]. A recent study examined the genetic influences in blepharospasm based on the examination of patients and their firstdegree relatives and found a very high proportion of probands (27%) with at least one first-degree relative affected by some form of focal dystonia [1]. Polymorphisms of the genes encoding TOR1A and D5 dopamine receptor (DRD5) have been associated with an increased lifetime risk of focal dystonia and these genes were investigated in two independent cohorts of Italian and North American patients with blepharospasm [2]. While no association was identified, analysis of the Italian group separately revealed an association with the same TOR1A risk haplotype as previously described in an Icelandic population. Over the last decade the number of dystonia loci and disease genes have grown dramatically [3]. The focal dystonia group consists of DYT1, DYT4, DYT6 and DYT7 but only three genes have been recognised up to now, TOR1A in DYT1, THAP1 in DYT6 and CIZ1 recently. THAP1 mutations are associated with a number of dystonia phenotypes, variability in severity and progression. In the dystonia cases that have been analysed so far, a handful of dystonia cases have been identified where blepharospasm was part of an overall segmental or generalised dystonia phenotype but no cases with BEB had been reported. Based on the reported data we investigated the role of THAP1 gene in blepharospasm in a Greek patient series. All patients and healthy controls that participated in the study gave informed consent and the study was approved by the local ethics committee of the University Hospital in Larissa, Greece. The diagnosis of blepharospasm was based on accepted criteria. Secondary causes such as structural lesions, trauma or exposure to toxic or neuroleptic substances were excluded. All patients