title: Intrafamilial variability of the primary dystonia DYT6 phenotype caused by p.Cys5Trp mutation in THAP1 gene.
abstract: Mutations localized in THAP1 gene, locus 18p11.21 have been reported as causative of primary dystonia type 6 (DYT6). Disease which is characterized mainly by focal dystonia, frequently involving the craniocervical region, however associated also with early-onset generalized dystonia and spasmodic dysphonia. Here we report a novel mutation in the THAP1 gene identified in a Polish family with DYT6 phenotype - the c.15C>G substitution in exon 1 introducing the missense mutation p.Cys5Trp within the N-terminal THAP domain. The mutation was described in two generations, in patients showing a broad spectrum of focal and generalized dystonia symptoms of variable onset. Our results indicate that certain mutations in the THAP1 gene may lead to primary dystonia with remarkable intrafamilial clinical variability.
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland. Electronic address: martajurek@wp.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Jurek
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Hoffman-Zacharska
authors.affiliation: Department of Neurology, Faculty of Heath Science, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Koziorowski
authors.affiliation: Department of Neurology, Faculty of Heath Science, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Mądry
authors.affiliation: Department of Neurology, Faculty of Heath Science, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Friedman
authors.affiliation: Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Bal
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D020821:Dystonic Disorders / Q000235:genetics*; D005192:Family Health; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D011044:Poland
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C474080:THAP1 protein, human
keywords: DYT6; Phenotypical variability; Reduced penetrance; THAP1