RESUMO
BACKGROUND: Prior studies suggest that dystonia is comorbid with affective disorders. This comorbidity could be a reaction to a chronic debilitating disorder or expression of a predisposing gene. The authors took advantage of the identification of a gene for dystonia, DYT1, to test these alternative explanations. METHODS: The authors administered a standardized psychiatric interview to members of families with an identified DYT1 mutation. The authors classified family members into three groups: mutation carriers with dystonia (manifesting carriers; n = 96), mutation carriers without dystonia (non-manifesting carriers; n = 60), and noncarriers (n = 65). RESULTS: The risk for recurrent major depressive disorder was increased in both non-manifesting carriers (RR = 4.95, CI = 1.72 to 14.29) and manifesting carriers (RR = 3.62, CI = 1.00 to 10.53) compared with noncarriers. Mutation carriers also had earlier age at onset of recurrent major depressive disorder than noncarriers. The severity of motor signs was not associated with the likelihood of recurrent depression. Mutation carriers did not have an increased risk for other affective disorders, such as single major depression or bipolar disorder. CONCLUSIONS: Early-onset recurrent major depression is associated with the DYT1 GAG mutation and this association is independent of motor manifestations of dystonia. These findings suggest that early-onset recurrent depression is a clinical expression of the DYT1 gene mutation.
Assuntos
Transtorno Depressivo/genética , Distonia Muscular Deformante/genética , Chaperonas Moleculares/fisiologia , Adulto , Idade de Início , Transtorno Depressivo/epidemiologia , Distonia Muscular Deformante/etnologia , Distonia Muscular Deformante/psicologia , Saúde da Família , Feminino , Heterozigoto , Humanos , Judeus/genética , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares/genética , Recidiva , Risco , Índice de Gravidade de Doença , Método Simples-CegoRESUMO
Myoclonus-dystonia (M-D) is an autosomal dominant disorder characterized by myoclonic and dystonic muscle contractions that are often responsive to alcohol. The dopamine D2 receptor gene (DRD2) on chromosome 11q has been implicated in one family with this syndrome, and linkage to a 28-cM region on 7q has been reported in another. We performed genetic studies, using eight additional families with M-D, to assess these two loci. No evidence for linkage was found for 11q markers. However, all eight of these families showed linkage to chromosome 7 markers, with a combined multipoint LOD score of 11.71. Recombination events in the families define the disease gene within a 14-cM interval flanked by D7S2212 and D7S821. These data provide evidence for a major locus for M-D on chromosome 7q21.
Assuntos
Cromossomos Humanos Par 7/genética , Distonia/genética , Ligação Genética/genética , Mioclonia/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 11/genética , Éxons/genética , Feminino , Marcadores Genéticos/genética , Humanos , Escore Lod , Masculino , Linhagem , Receptores de Dopamina D2/genética , Recombinação Genética/genética , SoftwareRESUMO
Essential myoclonus-dystonia is a neurological condition characterized by myoclonic and dystonic muscle contractions and the absence of other neurological signs or laboratory abnormalities; it is often responsive to alcohol. The disorder may be familial with apparent autosomal dominant inheritance. We report a large kindred with essential familial myoclonus-dystonia and map a locus for the disorder to a 28-cM region of chromosome 7q21-q31.
