Asunto(s)
Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Distrofias Musculares/genética , Distrofias Musculares/patología , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/patología , Humanos , Cuerpos de Inclusión Intranucleares/genética , Cuerpos de Inclusión Intranucleares/patología , Masculino , Músculo Esquelético/patología , Distrofias Musculares/complicaciones , Enfermedades Neurodegenerativas/complicaciones , Linaje , Expansión de Repetición de TrinucleótidoAsunto(s)
Enfermedades del Sistema Nervioso Autónomo/complicaciones , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedad por Cuerpos de Lewy/complicaciones , Enfermedad por Cuerpos de Lewy/patología , Anciano de 80 o más Años , Pueblo Asiatico/etnología , Autopsia , Diagnóstico Diferencial , Humanos , MasculinoRESUMEN
Autosomal dominant choreas are genetically heterogeneous disorders including Huntington disease (HD), Huntington disease like 1 (HDL1), Huntington disease like 2 (HDL2), dentatorubro-pallidoluysian atrophy (DRPLA), spinocerebellar ataxia type 17 (SCA17) and benign hereditary chorea (BHC). We identified two Japanese families with adult-onset benign chorea without dementia inherited in an autosomal dominant pattern. All affected individuals presented slowly progressive choreic movements in their upper and lower extremities, trunk and head with an age of onset ranging from 40 to 66 (average 54.3), which were markedly improved by haloperidol. The affected individuals also developed reduced muscle tones in their extremities. The findings obtained in the brain CT or MRI studies of nine affected individuals were normal. These clinical features resemble those of the so-called 'senile chorea'. HD, HDL1, HDL2, DRPLA, SCA17 and BHC caused by mutations in the TITF-1 gene were excluded by mutational and linkage analyses. A genome-wide linkage analysis revealed linkage to chromosome 8q21.3-q23.3 with a maximum cumulative two-point log of the odds (LOD) score of 4.74 at D8S1784 (theta = 0.00). Haplotype analysis of both the families defined the candidate region as 21.5 Mb interval flanked by M9267 and D8S1139. We named this adult-onset dominant inherited chorea 'benign hereditary chorea type 2 (BHC2)'.
Asunto(s)
Corea/genética , Cromosomas Humanos Par 8/genética , Anciano , Anciano de 80 o más Años , Corea/diagnóstico por imagen , Corea/patología , Mapeo Cromosómico , Femenino , Ligamiento Genético , Humanos , Escala de Lod , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Linaje , Tomografía Computarizada por Rayos XRESUMEN
To elucidate the etiology of chorea, we performed gene diagnoses of 79 consecutive cases of the disease (34 males, 45 females; age 15-79 years), which include 39 familial cases (37 pedigrees) and 40 sporadic cases, from 1997 to 2002, after their informed consent was obtained. We extracted genomic DNA from peripheral white blood cells, and performed genetic tests for Huntington disease (HD), dentatorubral pallidoluysian atrophy (DRPLA), Huntington disease like 1 (HDL1), HDL2 and spinocerebellar ataxia type 17 (SCA17). We found 37 cases (36 pedigrees) of HD, seven cases (seven pedigrees) of DRPLA. No cases of HDL1, HDL2 and SCA17 were found. We also found three cases (two pedigrees) presenting an autosomal dominant trait with an unknown origin, and two cases whose parents were consanguineously related. Therefore, further genetic heterogeneity is expected in the cases of chorea in Japan.