RESUMO
BACKGROUND: Recently, a novel mutation in exon 24 of DNAJC13 gene (p.Asn855Ser, rs387907571) has been reported to cause autosomal dominant Parkinson's disease (PD) in a multi-incident Mennonite family. METHODS: In the present study the mutation containing exon of the DNAJC13 gene has been sequenced in a Caucasian series consisting of 1938 patients with clinical PD and 838 with pathologically diagnosed Lewy body disease (LBD). RESULTS: Our sequence analysis did not identify any coding variants in exon 24 of DNAJC13. Two previously described variants in intron 23 (rs200204728 and rs2369796) were observed. CONCLUSION: Our results indicate that the region surrounding the DNAJC13 p.Asn855Ser substitution is highly conserved and mutations in this exon are not a common cause of PD or LBD among Caucasian populations.
Assuntos
Doença por Corpos de Lewy/genética , Chaperonas Moleculares/genética , Doença de Parkinson/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Europa (Continente) , Éxons , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , MutaçãoRESUMO
BACKGROUND: Previous epidemiologic and genetic studies have suggested a link between Parkinson disease (PD), essential tremor (ET), and restless legs syndrome (RLS). METHODS: We describe the clinical, PET, and pathologic characteristics of an extensive kindred from Arkansas with hereditary PD, ET, and RLS. The pedigree contains 138 individuals. Sixty-five family members were examined neurologically up to 3 times from 2004 to 2010. Clinical data were collected from medical records and questionnaires. Genetic studies were performed. Five family members underwent multitracer PET. Two individuals with PD were examined postmortem. RESULTS: Eleven family members had PD with generally mild and slowly progressive symptoms. Age at onset was between 39 and 74 years (mean 59.1, SD 13.4). All individuals treated with l-dopa responded positively. Postural or action tremor was present in 6 individuals with PD, and in 19 additional family members. Fifteen persons reported symptoms of RLS. PET showed reduced presynaptic dopamine function typical of sporadic PD in a patient with PD and ET, but not in persons with ET or RLS. The inheritance pattern was autosomal dominant for PD and RLS. No known pathogenic mutation in PD-related genes was found. Fourteen of the family members with PD, ET, or RLS had depression. Neuropathologic examination revealed pallidonigral pigment spheroid degeneration with ubiquitin-positive axonal spheroids, TDP43-positive pathology in the basal ganglia, hippocampus, and brainstem, and only sparse Lewy bodies. CONCLUSION: Familial forms of PD, ET, RLS, and depression occur in this family. The genetic cause remains to be elucidated.
Assuntos
Depressão/complicações , Tremor Essencial/complicações , Saúde da Família , Transtornos Parkinsonianos/complicações , Síndrome das Pernas Inquietas/complicações , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/patologia , Proteínas de Ligação a DNA/metabolismo , Depressão/diagnóstico por imagem , Depressão/genética , Complexo Dinactina , Tremor Essencial/diagnóstico por imagem , Tremor Essencial/genética , Fator de Iniciação Eucariótico 4G/genética , Feminino , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Estudos Longitudinais , Masculino , Entrevista Psiquiátrica Padronizada , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Transtornos Parkinsonianos/diagnóstico por imagem , Transtornos Parkinsonianos/genética , Tomografia por Emissão de Pósitrons/métodos , Proteínas Serina-Treonina Quinases/genética , Síndrome das Pernas Inquietas/diagnóstico por imagem , Síndrome das Pernas Inquietas/genética , alfa-Sinucleína/genéticaRESUMO
OBJECTIVE: To report genealogic, clinical, imaging, neuropathologic, and genetic data from a Canadian kindred with dystonia and brain calcinosis originally described in 1985. METHODS: The authors performed clinical examinations and CT and PET studies of the head and analyzed blood samples. One autopsy was performed. RESULTS: The family tree was expanded to 166 individuals. No individuals were newly affected with dystonia, but postural tremor developed in two. The mean age at symptom onset was 19 years. Eight individuals had dystonia: three focal, one segmental, one multifocal, and three generalized. Seven displayed additional signs: chorea, intellectual decline, postural tremor, and dysarthria. CT studies were performed on five affected and 10 at-risk family members. All affected individuals and eight at-risk individuals had brain calcinosis. PET scans in two individuals showed reduced D(1)- and D(2)-receptor binding and reduced uptake of 6-[(18)F]fluoro-l-dopa. Autopsy of one affected individual showed extensive depositions of calcium in the basal ganglia, thalamus, cerebral white matter, and cerebellum. No specific immunohistochemistry abnormalities were seen. Genome search data showed no evidence of linkage to the previously described loci IBGC1, DYT1, and DYT12. CONCLUSIONS: The phenotype of this family consists of dystonia-plus syndrome. Brain calcium deposits vary in severity and distribution, suggesting that calcifications alone are not entirely responsible for the observed clinical signs. Further studies are needed to elucidate the etiology of this heterogeneous group of disorders.
Assuntos
Encefalopatias/epidemiologia , Encefalopatias/genética , Calcinose/epidemiologia , Calcinose/genética , Cromossomos Humanos Par 14/genética , Distúrbios Distônicos/epidemiologia , Distúrbios Distônicos/genética , Adolescente , Adulto , Idoso , Canadá/epidemiologia , Criança , Transtornos Cromossômicos/epidemiologia , Transtornos Cromossômicos/genética , Comorbidade , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Prevalência , Medição de Risco/métodos , Fatores de RiscoRESUMO
Since the original 1995 report of a parkinsonian kindred, four individuals have been affected (mean age at onset, 65 years). All four had cardinal signs of Parkinson disease (PD) and good response to levodopa. Four autopsies showed neuronal loss and gliosis in the substantia nigra. Lewy bodies (LB) limited to brainstem nuclei were detected in one case, diffuse LB in the second, neurofibrillary tangles (NFT) without LB in the third, and neither NFT nor LB in the fourth. Genetic studies suggested linkage to the PARK8 locus on chromosome 12.
Assuntos
Proteínas do Tecido Nervoso/genética , Transtornos Parkinsonianos/genética , Tauopatias/genética , Idoso , Encéfalo/patologia , Cromossomos Humanos Par 12/genética , Família , Feminino , Seguimentos , Ligação Genética , Variação Genética , Humanos , Imuno-Histoquímica , Corpos de Lewy/patologia , Masculino , Mutação , Transtornos Parkinsonianos/diagnóstico , Transtornos Parkinsonianos/patologia , Linhagem , Fenótipo , Substância Negra/patologia , Sinucleínas , Ubiquitina-Proteína Ligases/genética , Proteínas tau/genéticaRESUMO
OBJECTIVES: Determine the long-term efficacy of thalamic deep brain stimulation (DBS) for treatment of tremor among individuals with tremor-predominant Parkinson's disease (PD).Design. Longitudinal, unblinded assessment of tremor and activities of daily living (ADL) at baseline (pre-surgical), and post-operative intervals of 1, 3, and 12 months, and annually thereafter up to 3 years. METHODS: A clinical series of 19 individuals undergoing placement of a DBS system for treatment of PD-related tremor. A battery of subjective and objective measures of tremor was completed at planned pre- and post-operative intervals. RESULTS: Stimulation was associated with significant improvement on subjective and objective measures of ADL performance, midline tremor, and contralateral upper and lower extremity tremor, including parkinsonian resting and action tremors, over the follow-up period. Ipsilateral tremor showed little or no effect of stimulation after the first 3 months. Antiparkinsonian medication use and stimulation parameters showed little or no change over the course of follow-up. About half (53%) of all individuals reported at least one side effect, generally mild, during the follow-up period, with paresthesias and dysarthria being the most common. A total of two leads required replacement due to (1) infection, and (2) adverse side effects (i.e. burning and tingling with stimulation). CONCLUSION: DBS is associated with stable tremor control in PD. Side-effects are typically easily managed with stimulation adjustments, although in some cases lead replacement may be required.
Assuntos
Terapia por Estimulação Elétrica/métodos , Doença de Parkinson/terapia , Tálamo/fisiologia , Tremor/terapia , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Estatísticas não Paramétricas , Tálamo/cirurgia , Tremor/complicaçõesRESUMO
The authors prospectively collected unblinded data from 27 consecutive patients following thalamic stimulation. A significant reduction of midline tremor was achieved after unilateral surgery, but a staged contralateral surgery had an additional effect. A subgroup analysis showed significant beneficial effects for head, voice, tongue, and face tremor. The most frequent reversible side effects were disequilibrium, dysarthria, and paresthesias. We observed more pulse generator adjustments for speech problems in the bilaterally implanted group.