The role of DYT1 in primary torsion dystonia in Europe

• Published in: Brain (London, England : 1878) Vol. 121; no. 12; pp. 2335 - 2339
• Main Authors: VALENTE, E. M, WARNER, T. T, JARMAN, P. R, MATHEN, D, FLETCHER, N. A, MARSDEN, C. D, BHATIA, K. P, WOOD, N. W
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.12.1998; Oxford Publishing Limited (England)
• Subjects: Adolescent; Adult; Base Sequence - genetics; Biological and medical sciences; Carrier Proteins - genetics; Carrier Proteins - physiology; Child; Chromosome Mapping; Dystonia - genetics; Dystonia - physiopathology; Female; Gene Deletion; Genotype; Humans; Male; Medical sciences; Middle Aged; Molecular Chaperones; Mutation - genetics; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Pedigree; Phenotype; Torsion Abnormality; Human; Nervous system diseases; Exploration; Genetic disease; Involuntary movement; Polymerase chain reaction; Heterogeneity; Striated muscle disease; Deletion; Dystonia; Mutation; Molecular biology; Neurological disorder; Torsion; Extrapyramidal syndrome
• ISSN: 0006-8950; 1460-2156; 1460-2156
• DOI: 10.1093/brain/121.12.2335

Primary torsion dystonia (PTD) is a clinically and genetically heterogeneous movement disorder. DYT1 on chromosome 9q34 was the first PTD gene to be mapped. A 3-bp (GAG) deletion in this gene was reported to account for almost all early limb-onset generalized PTD. No relationship has been found with DYT1 in patients with prominent craniocervical involvement. To elucidate the DYT1-associated phenotype, we analysed the DYT1 mutation in 150 PTD patients, either sporadic or index cases from small PTD families. Twenty-two patients were positive for the GAG deletion in the DYT1 gene. Fifteen of them presented with the typical DYT1 phenotype (early, limb-onset generalized dystonia without spread to craniocervical muscles), four had limb-onset dystonia with spread to craniocervical muscles, two patients had arm-onset segmental dystonia and one had focal right-arm dystonia. One-hundred and twenty-eight patients were negative for the DYT1 mutation. Forty-six of them had segmental dystonia and 59 had focal dystonia. The other 23 patients presented with generalized dystonia, either with craniocervical involvement (13 patients) or without spread to the craniocervical region (typical DYT1 phenotype-10 patients). These data confirm the importance of the GAG deletion in European cases of PTD, and indicate phenotypic and genotypic heterogeneity.