LINKAGE STUDIES IN ALCOHOL-RESPONSIVE MYOCLONIC DYSTONIA

A large German family with ''myoclonic dystonia with lightning jerks r esponsive to alcohol'' was identified. Eleven affected pedigree member s and six obligate gene carriers from five generations were identified . A description of one branch of this pedigree was published in 1964. Our examination 30 years after the initial report confirms the clinica l syndrome of a nonprogressive movement disorder characterized by myoc lonic jerks affecting the proximal muscles and the muscles of the trun k, accompanied by mild dystonic features in some affected family membe rs. Segregation analysis favors autosomal dominant inheritance with hi gh, but incomplete, penetrance in males and much lower penetrance in f emales. Linkage analysis was performed using simple sequence repeat po lymorphisms (CA repeats) closely associated with or spanning the chrom osomal regions containing 15 candidate genes: the gene for early-onset generalized torsion dystonia, DYT1 (chromosome 9q34); the genes for s ubunits alpha 2, beta 1, and gamma 1 (chromosome 4p12-4q13); for alpha 1, alpha 6, beta 2, and gamma 2 (chromosome 5q31.1-5q31.3); for alpha 4, alpha 5, beta 3, and gamma 3 (chromosome 15q11-15q13); for rho 1 a nd rho 2 (chromosome 6q14-6q21) of the gamma-aminobutyric acid A recep tor; and for the alpha subunit of the glycine receptor (chromosome 5q3 1). By a combination of pairwise and multipoint linkage analysis, it c ould be excluded that any of these candidate gene-bearing chromosomal regions contain the disease gene in this family. We also excluded majo r portions of three chromosomal regions syntenic with mouse chromosome 3, which carries the murine beta subunit of the glycine receptor.