title: Mutation screening of the DYT6/THAP1 gene in Italy.
abstract: Mutations in the THAP1 gene on chromosome 8p21-p22 (DYT6 locus) have been recently reported as causative of autosomal dominant primary torsion dystonia (PTD) in four Amish-Mennonite families and in 12 additional probands of different ancestry. We sequenced the THAP1 gene in 158 patients with DYT1-negative PTD who had onset of symptoms below 30 years and/or positive family history. One sporadic Greek male patient, aged 57 years, was found to carry a novel heterozygous missense variant in THAP1 exon 3 (p.Cys170Arg), of likely pathogenic significance. This subject first presented with right writer's cramp at age of 10 years and, subsequently, developed left arm dystonia and an extremely severe left laterocollis, without further spreading to other body districts. Our findings expand the genotypic spectrum of THAP1 and strengthen the association with upper body involvement, including the cranial and cervical districts that are usually spared in DYT1-PTD.
authors.affiliation: IRCCS Casa Sollievo della Sofferenza, CSS-Mendel Institute, Rome, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Bonetti
authors.forename: Chiara
authors.initials: C
authors.lastname: Barzaghi
authors.forename: Francesco
authors.initials: F
authors.lastname: Brancati
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ferraris
authors.forename: Emanuele
authors.initials: E
authors.lastname: Bellacchio
authors.forename: Alessandro
authors.initials: A
authors.lastname: Giovanetti
authors.forename: Tamara
authors.initials: T
authors.lastname: Ialongo
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zorzi
authors.forename: Carla
authors.initials: C
authors.lastname: Piano
authors.forename: Martina
authors.initials: M
authors.lastname: Petracca
authors.forename: Alberto
authors.initials: A
authors.lastname: Albanese
authors.forename: Nardo
authors.initials: N
authors.lastname: Nardocci
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Bentivoglio
authors.forename: Barbara
authors.initials: B
authors.lastname: Garavaglia
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D004422:Dystonia Musculorum Deformans / Q000235:genetics*; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007223:Infant; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C474080:THAP1 protein, human