title: Genetic testing for early-onset torsion dystonia (DYT1): introduction of a simple screening method, experiences from testing of a large patient cohort, and ethical aspects.
abstract: Early-onset, generalized primary torsion dystonia (PTD) is an autosomal dominantly inherited disorder, characterized by involuntary movements and abnormal postures. The majority of cases are caused by a 3-bp deletion in the DYT1 gene on chromosome 9q34 that allows for specific genetic testing. We developed a simple, reliable, and cost-effective, PCR-based screening method for this mutation. Testing results from a cohort of 550 cases, including patients with different forms of dystonia and unclassified movement disorders, revealed that 72.2% of the patients with typical early-onset generalized PTD carried the GAG deletion in the DYT1 gene. Among 300 cases with late-onset focal/segmental dystonia, only 3 patients tested positive for the GAG deletion whereas 12.8% of the patients with an unclassified movement disorder were GAG positive. Our results confirm a genotype/phenotype correlation in early-onset PTD and show that application of strict clinical criteria leads to accurate prediction of carrier status in more than two-thirds of patients with this type of dystonia. Currently, we suggest that testing be recommended in individuals with age of onset of dystonia below 30 years and/or a positive family history of early-onset PTD. Testing is not recommended in patients with onset of symptoms after 30 years or in asymptomatic individuals under the age of 18.
authors.affiliation: Neurology Department, Massachusetts General Hospital, Boston, USA.
authors.forename: C
authors.initials: C
authors.lastname: Klein
authors.forename: J
authors.initials: J
authors.lastname: Friedman
authors.forename: S
authors.initials: S
authors.lastname: Bressman
authors.forename: P
authors.initials: P
authors.lastname: Vieregge
authors.forename: M F
authors.initials: MF
authors.lastname: Brin
authors.forename: P P
authors.initials: PP
authors.lastname: Pramstaller
authors.forename: D
authors.initials: D
authors.lastname: De Leon
authors.forename: J
authors.initials: J
authors.lastname: Hagenah
authors.forename: M
authors.initials: M
authors.lastname: Sieberer
authors.forename: C
authors.initials: C
authors.lastname: Fleet
authors.forename: R
authors.initials: R
authors.lastname: Kiely
authors.forename: W
authors.initials: W
authors.lastname: Xin
authors.forename: X O
authors.initials: XO
authors.lastname: Breakefield
authors.forename: L J
authors.initials: LJ
authors.lastname: Ozelius
authors.forename: K B
authors.initials: KB
authors.lastname: Sims
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004421:Dystonia / Q000208:ethnology / Q000235:genetics*; D004992:Ethics, Medical; D005260:Female; D005820:Genetic Testing / Q000379:methods* / Q000523:psychology; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007585:Jews; D008297:Male; D018832:Molecular Chaperones; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D011296:Prenatal Diagnosis; D017384:Sequence Deletion; D018911:Trinucleotide Repeats / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D018832:Molecular Chaperones; C108175:TOR1A protein, human