Dystonia genetics (AAN report)

Subject: Dystonia genetics (AAN report)

Date: 4/23/1999

1. The DYT1 phenotype
D Raymond, SB Bressman, C Sabatti, D de Leon, C Klein, S Fahn, R Saunders-Pullman, MF Brin, PL Kramer, XO Breakefield, LJ Ozelius, NJ Risch
Neurology 1999;52(Suppl 2):A116-117

The GAG deletion of the DYT1 gene leads to similar phenotypes in Ashkenazi and non-Ashkenazi patients, marked by early limb onset and spread to other limbs and axial muscles, according to this analysis of 329 patients with primary torsion dystonia. Of the 176 carriers, 96% had limb onset, and 74% had spread to limbs and other axial muscles, but only 11% had spread to cranial muscles. No significant differences were found between Ashkenazi and non-Ashkenazi patients, except in carrier frequency (82% vs. 53% of early-onset cases). The authors write, "Based on our findings, DYT1 testing is recommended for all individuals with early-onset PTD and those with onset between ages 28 and 45 years beginning in a limb."

2. The GAG deletion of the DYT-1 gene is infrequent in occupational cramp
ME Charness, C Klein, H Woodward, LJ Ozelius, XO Breakefield, RL Friedman
Neurology 1999;52(Suppl 2):A117

Genetic analysis of 14 musicians with occupational cramp of an upper extremity or the face revealed no GAG deletion in the DYT1 gene, including in two sisters with a family history of focal dystonia. The deletion was found in one patient with writer's cramp.

3. A novel mitochondrial DNA mutation in a patient with dystonia, stroke-like episodes and cataracts
DK Simon, M Tarnopolsky, DR Johns
Neurology 1999;52(Suppl 2):A119-120

A new mitochondrial DNA mutation may be responsible for a dystonia syndrome in a 30-year-old woman, according to this study. The mutation is a frame shift in the initiating methionine sequence of the gene encoding a complex I subunit. The mutation was absent in 100 normal controls, and present in three asymptomatic family members.

4. Two families with rapid-onset dystonia-parkinsonism link to chromosome 19
PL Kramer, C Klein, K Schilling, LJ Ozelius, M Mineta, MR Farlow, D de Leon, XO Breakefield, SB Bressman, WB Dobyns, A Brashear
Neurology 1999;52(Suppl 2):A13

5. Rapid-onset dystonia-parkinsonism: A new kindred
SJ Pittock, DW Webb, O Hardiman
Neurology 1999;52(Suppl 2):A120

Three new families with rapid-onset dystonia-parkinsonism are described, two from the United States and one from Ireland. Levodopa was ineffective in all three families. Kramer et al. report linkage to 19q13 in both American families, with no known common ancestry. In one American family, several members with only mild limb dystonia carried no part of the haplotype. The authors suggest that unaffected members with the haplotype represent incomplete penetrance, while the cases of mild dystonia may indicate a moderating gene elsewhere.

E-MOVE Editor: Richard Robinson, NASW, WE MOVE

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