Association of a missense change in the D2 dopamine receptor with myoclonus dystonia

Christine Klein, Mitchell F. Brin, Patricia Kramer, Miguel Sena-Esteves, Deborah De Leon, Dana Doheny, Susan Bressman, Stanley Fahn, Xandra O. Breakefield, Laurie J. Ozelius*

*Corresponding author for this work
99 Citations (Scopus)


Hereditary autosomal dominant myoclonus dystonia (MD) is a movement disorder characterized by involuntary lightning jerks and dystonic movements and postures alleviated by alcohol. Although various large families with MD have been described, no positive linkage has been found to a chromosomal location. We report a family with eight members with MD. Linkage analysis identified a 23-centimorgan region on chromosome 11q23 that cosegregates with the disease state (maximum multipoint logarithm of odds score = 2.96 at D11S897). This region contains an excellent candidate gene for involvement in the etiology of MD, the D2 dopamine receptor (DRD2) gene. Neurotransmission mediated by DRD2 is known to have a key role in the control of movement and also has been implicated in reward and reinforcement mechanisms and psychiatric disorders. Sequencing of the coding region of DRD2 indicated that all affected and obligate carriers were heterozygous for a Val154Ile change in exon 3 of the protein, which is highly conserved across species. This change was found neither in other unaffected members of the pedigree nor in 250 control chromosomes. Our finding provides evidence for the involvement of DRD2 in a disorder of the central nervous system and should lead to further insight into the function of the dopaminergic system in dystonia and other movement and mood disorders.

Original languageEnglish
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number9
Pages (from-to)5173-5176
Number of pages4
Publication statusPublished - 27.04.1999


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