RESUMO
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.
Assuntos
Saúde da Família , Ligação Genética , Distrofia Muscular de Emery-Dreifuss/genética , Sarcoglicanas/genética , Síndrome de Tourette/genética , Adolescente , Adulto , Idoso , Criança , Análise Mutacional de DNA/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Distúrbios Distônicos/genética , Predisposição Genética para Doença/genética , Chaperonas Moleculares/genética , Mutação/genética , Adulto , Idoso , Cromossomos Humanos Par 9/genética , Análise Mutacional de DNA , Progressão da Doença , Distúrbios Distônicos/metabolismo , Distúrbios Distônicos/fisiopatologia , Meio Ambiente , Saúde da Família , Feminino , Marcadores Genéticos/genética , Testes Genéticos , Variação Genética/genética , Haplótipos , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Penetrância , Fenótipo , IugosláviaRESUMO
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.
Assuntos
Análise Mutacional de DNA , Triagem de Portadores Genéticos , Transtornos Parkinsonianos/genética , Proteínas Serina-Treonina Quinases/genética , Adulto , Fatores Etários , Alelos , Dominância Cerebral/fisiologia , Ecoencefalografia , Éxons , Feminino , Marcadores Genéticos/genética , Testes Genéticos , Genótipo , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Masculino , Pessoa de Meia-Idade , Transtornos Parkinsonianos/diagnóstico , Fenótipo , Polimorfismo de Fragmento de Restrição , Polimorfismo Conformacional de Fita Simples , RecidivaRESUMO
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.
Assuntos
Análise Mutacional de DNA , Doença de Parkinson/genética , Síndrome das Pernas Inquietas/genética , Ubiquitina-Proteína Ligases/genética , Adulto , Idoso , Aberrações Cromossômicas , Mapeamento Cromossômico , Comorbidade , Progressão da Doença , Feminino , Dosagem de Genes , Genes Dominantes , Humanos , Escore Lod , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Exame Neurológico , Doença de Parkinson/diagnóstico , Linhagem , Fenótipo , Polimorfismo Conformacional de Fita Simples , Síndrome das Pernas Inquietas/diagnósticoRESUMO
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.
Assuntos
Síndrome do Cromossomo X Frágil/genética , Ligação Genética/genética , Proteínas do Tecido Nervoso/genética , Doença de Parkinson/genética , Proteínas de Ligação a RNA/genética , Ubiquitina-Proteína Ligases/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Análise Mutacional de DNA , Feminino , Proteína do X Frágil da Deficiência Intelectual , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/patologia , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Fatores Sexuais , Repetições de Trinucleotídeos/genéticaRESUMO
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.
Assuntos
Síndrome Maligna Neuroléptica/genética , Adolescente , Adulto , Antipsicóticos/efeitos adversos , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Linhagem , Prevalência , Esquizofrenia/tratamento farmacológicoRESUMO
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.