PMID- 10220438
OWN - NLM
STAT- MEDLINE
DCOM- 19990610
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 9
DP  - 1999 Apr 27
TI  - Association of a missense change in the D2 dopamine receptor with myoclonus
      dystonia.
PG  - 5173-6
AB  - 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.
FAU - Klein, C
AU  - Klein C
AD  - Molecular Neurogenetics Unit, Neurology Service, Massachusetts General Hospital
      and Department of Neurology, Harvard Medical School, Boston, MA 02114, USA.
FAU - Brin, M F
AU  - Brin MF
FAU - Kramer, P
AU  - Kramer P
FAU - Sena-Esteves, M
AU  - Sena-Esteves M
FAU - de Leon, D
AU  - de Leon D
FAU - Doheny, D
AU  - Doheny D
FAU - Bressman, S
AU  - Bressman S
FAU - Fahn, S
AU  - Fahn S
FAU - Breakefield, X O
AU  - Breakefield XO
FAU - Ozelius, L J
AU  - Ozelius LJ
LA  - eng
GR  - R01 NS028384/NS/NINDS NIH HHS/United States
GR  - NS28384/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Receptors, Dopamine)
SB  - IM
MH  - Adolescent
MH  - Amino Acid Sequence
MH  - Child
MH  - Child, Preschool
MH  - Dystonia/*genetics
MH  - Genetic Linkage
MH  - Humans
MH  - Male
MH  - Molecular Sequence Data
MH  - *Mutation, Missense
MH  - Myoclonus/*genetics
MH  - Pedigree
MH  - Receptors, Dopamine/*genetics
MH  - Sequence Alignment
PMC - PMC21836
EDAT- 1999/04/29 00:00
MHDA- 1999/04/29 00:01
CRDT- 1999/04/29 00:00
PHST- 1999/04/29 00:00 [pubmed]
PHST- 1999/04/29 00:01 [medline]
PHST- 1999/04/29 00:00 [entrez]
AID - 10.1073/pnas.96.9.5173 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5173-6. doi: 10.1073/pnas.96.9.5173.