Mutation screening of the DYT6/THAP1 gene in Italy.
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.
Bonetti
Monica
M
IRCCS Casa Sollievo della Sofferenza, CSS-Mendel Institute, Rome, Italy.
Barzaghi
Chiara
C
Brancati
Francesco
F
Ferraris
Alessandro
A
Bellacchio
Emanuele
E
Giovanetti
Alessandro
A
Ialongo
Tamara
T
Zorzi
Giovanna
G
Piano
Carla
C
Petracca
Martina
M
Albanese
Alberto
A
Nardocci
Nardo
N
Dallapiccola
Bruno
B
Bentivoglio
Anna Rita
AR
Garavaglia
Barbara
B
Valente
Enza Maria
EM
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
D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C474080:THAP1 protein, human