Linkage studies in alcohol‐responsive myoclonic dystonia

A large German family with “myoclonic dystonia with lightning jerks responsive to alcohol” was identified. Eleven affected pedigree members 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 clinical syndrome of a nonprogressive movement disorder charcterized by myoclonic jerks affecting the proximal muscles and the muscles of the trunk, accompanied by mild dystonic features in some affected family members. Segregation analysis favors autosomal dominant inheritance with high, but incomplete, penetrance in males and much lower penetrance in females. Linkage analysis was performed using simple sequence repeat polymorphisms ( CA repeats) closely associated with or spanning the chromosomal regions containing 15 candidate genes: the gene for early‐onset generalized torsion dystonia, DYTI (chromosome 9q34); the genes for subunits α2, β1, and γ1 (chromosome 4p12–4q13);for α1,α6,β2 and γ2(chromosome 5q31.1–5q31.3); for α4,α5,β3, and γ3 (chromosome 15q11–15q13); for ρ1 and ρ2 (chromosome 6q14–6q21) of the gamma‐aminobutyric acid A receptor; and for the alpha subunit of the glycine receptor (chromosome 5q31). By a combination of pairwise and multipoint linkage analysis, it could be excluded that any of these candidate gene bearing chromosomal regions contain the disease gene in this family. We also excluded major portions of three chromosomal regions syntenic with mouse chromosome 3, which carries the murine beta subunit of the glycine receptor.