RESUMEN
UNLABELLED: The objective of this study was to report clinical details and results of genetic testing for mutations in the epsilon-sarcoglycan (SGCE) gene, the Slit and Trk-like 1 (SLITRK1) gene and for linkage to the DYT15, DYT1, and DRD2 gene loci in a family with autosomal dominant myoclonus-dystonia (M-D) and Gilles de la Tourette syndrome (GTS). Fourteen family members, from three generations, underwent a detailed clinical assessment and donated DNA samples. The SGCE and the SLITRK1 gene were sequenced and investigated by gene dosage analysis in selected family members. Linkage to the SGCE, DYT15, DYT1, DRD2, and SLITRK1 loci was also tested. RESULTS: We included three healthy and 11 affected family members with M-D (n = 3), dystonia alone (n = 2), GTS (n = 1), tics (n = 1) or a combination of these with obsessive compulsive disorder (OCD) (M-D + OCD: n = 2; dystonia+OCD: n = 1; M-D + GTS + OCD: n = 1). There was no linkage to the SGCE, DYT15, DYT1 or DRD2 loci. No changes were found in the SLITRK1 gene. The presence of both M-D and GTS in one family, in which all known M-D loci and a recently discovered GTS locus were excluded, suggests a novel susceptibility gene for both M-D and GTS.
Asunto(s)
Salud de la Familia , Ligamiento Genético , Distrofia Muscular de Emery-Dreifuss/genética , Sarcoglicanos/genética , Síndrome de Tourette/genética , Adolescente , Adulto , Anciano , Niño , Análisis Mutacional de ADN/métodos , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Most cases of early-onset primary torsion dystonia are caused by the same 3-bp (GAG) deletion in the DYT1 gene. We describe a large Serbian family with significant intrafamilial variability of the DYT1 phenotype, from asymptomatic carrier status to late-onset focal, and generalized jerky dystonia. Seven mutation carriers (six proven by direct analysis and one by inferred haplotype) were identified, but only two of them were affected by dystonia (penetrance reduced to 29%). In addition, three GAG-deletion-negative family members also developed dystonia (two multifocal dystonia and one torticollis), suggesting that their involuntary movements are due to some other etiological factor(s) (i.e., another dystonia gene), or may be psychogenic.
Asunto(s)
Trastornos Distónicos/genética , Predisposición Genética a la Enfermedad/genética , Chaperonas Moleculares/genética , Mutación/genética , Adulto , Anciano , Cromosomas Humanos Par 9/genética , Análisis Mutacional de ADN , Progresión de la Enfermedad , Trastornos Distónicos/metabolismo , Trastornos Distónicos/fisiopatología , Ambiente , Salud de la Familia , Femenino , Marcadores Genéticos/genética , Pruebas Genéticas , Variación Genética/genética , Haplotipos , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Linaje , Penetrancia , Fenotipo , YugoslaviaRESUMEN
Mutations in LRRK2 (leucine-rich repeat kinase 2) have been associated with autosomal dominant Parkinson's disease (PD) and cluster in several 3' exons of the gene. The majority of mutations have been detected in late-onset cases (age at onset >50 years). We screened 5 of the 51 exons of LRRK2 that previously have been reported to harbor mutations in 98 early-onset and 42 late-onset PD patients. We identified two mutations (c.4321C>T, c.6055G>A) in three early-onset patients. Screening of an additional 220 early-onset PD patients for these mutations revealed another mutation carrier. In conclusion, LRRK2 mutations need to be considered also in early-onset PD.
Asunto(s)
Análisis Mutacional de ADN , Tamización de Portadores Genéticos , Trastornos Parkinsonianos/genética , Proteínas Serina-Treonina Quinasas/genética , Adulto , Factores de Edad , Alelos , Dominancia Cerebral/fisiología , Ecoencefalografía , Exones , Femenino , Marcadores Genéticos/genética , Pruebas Genéticas , Genotipo , Humanos , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Masculino , Persona de Mediana Edad , Trastornos Parkinsonianos/diagnóstico , Fenotipo , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo Conformacional Retorcido-Simple , RecurrenciaRESUMEN
Recent studies have suggested an association between restless legs syndrome (RLS) and Parkinson's disease (PD). We present a large multigenerational family and a smaller family with RLS. A Parkin mutation was found in 10 of 20 patients from both families with idiopathic RLS but was not considered causative. The clinical phenotype did not differ between RLS patients with and without a Parkin mutation. Inheritance of RLS was consistent with autosomal dominant transmission, and linkage analysis excluded all three known loci for RLS.
Asunto(s)
Análisis Mutacional de ADN , Enfermedad de Parkinson/genética , Síndrome de las Piernas Inquietas/genética , Ubiquitina-Proteína Ligasas/genética , Adulto , Anciano , Aberraciones Cromosómicas , Mapeo Cromosómico , Comorbilidad , Progresión de la Enfermedad , Femenino , Dosificación de Gen , Genes Dominantes , Humanos , Escala de Lod , Masculino , Repeticiones de Microsatélite/genética , Persona de Mediana Edad , Examen Neurológico , Enfermedad de Parkinson/diagnóstico , Linaje , Fenotipo , Polimorfismo Conformacional Retorcido-Simple , Síndrome de las Piernas Inquietas/diagnósticoRESUMEN
Premutations in the FMR1 gene may be associated with some cases of parkinsonism. To test this hypothesis, we determined the CGG repeat number in FMR1 in 673 individuals with and without parkinsonism and detected 3 premutation carriers (2 patients, 1 control). Of note, 1 of the affected premutation carriers had a heterozygous Parkin mutation.
Asunto(s)
Síndrome del Cromosoma X Frágil/genética , Ligamiento Genético/genética , Proteínas del Tejido Nervioso/genética , Enfermedad de Parkinson/genética , Proteínas de Unión al ARN/genética , Ubiquitina-Proteína Ligasas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Análisis Mutacional de ADN , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/patología , ARN Mensajero/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Factores Sexuales , Repeticiones de Trinucleótidos/genéticaRESUMEN
BACKGROUND: A genetic susceptibility to extrapyramidal symptoms caused by treatment with neuroleptic medication has been suggested. AIMS: To identify predictor variables for neuroleptic-induced extrapyramidal symptoms, particularly considering family history of primary movement disorders. METHOD: We investigated 100 in-patients receiving a stable neuroleptic medication with regard to occurrence of extrapyramidal symptoms, drug history and detailed family history of primary movement disorders. RESULTS: Step-wise logistic regression analysis revealed that a positive family history was a significant predictor for lifetime prevalence of extrapyramidal symptoms, including reported and currently observed symptoms. The duration of exposure to neuroleptic medication and age were further predictors. CONCLUSIONS: Our findings underline the notion of genetic susceptibility for secondary extrapyramidal symptoms and suggest possible shared genetic factors in primary and secondary movement disorders as well as psychotic disorders.
Asunto(s)
Síndrome Neuroléptico Maligno/genética , Adolescente , Adulto , Antipsicóticos/efectos adversos , Humanos , Modelos Logísticos , Persona de Mediana Edad , Linaje , Prevalencia , Esquizofrenia/tratamiento farmacológicoRESUMEN
Many cases of myoclonus-dystonia (M-D) are caused by mutations in the epsilon-sarcoglycan (SGCE) gene. We describe 3 children with a similar clinical picture of autosomal dominant M-D and an SGCE mutation in only one of them, suggesting that M-D is genetically heterogeneous.
