RESUMO
The COVID-19 pandemic has changed the face of healthcare delivery. This article discusses the concept of medical sacrifice and personal risk, and how healthcare workers can apply these concepts when working outside their comfort zones, while remaining within the limits of their clinical competence. Guidance from the General Medical Council and the medical defence organisations is reviewed and considered in its practical application. We explore how a medical student, now a 'fast tracked' junior doctor, and a senior consultant, with pre-existing health issues, can feel confident working as part of the NHS response to COVID-19.
Assuntos
Competência Clínica/legislação & jurisprudência , Imperícia/legislação & jurisprudência , Erros Médicos/legislação & jurisprudência , Corpo Clínico Hospitalar/legislação & jurisprudência , Má Conduta Profissional/legislação & jurisprudência , Tomada de Decisões , Disciplina no Trabalho , Humanos , Intenção , Licenciamento em Medicina , Imperícia/classificação , Erros Médicos/classificação , Nova Zelândia , Segurança do Paciente , Má Conduta Profissional/classificação , Reino UnidoRESUMO
We describe a sporadic case of atypical parkinsonism-dystonia of subacute onset at the age of 16 years in a male from a consanguineous family. He showed marked orofacial dystonia, levodopa-induced dyskinesia, and a stereotyped bilateral eye-pressing movement disorder. We combined Sanger sequencing of candidate genes, homozygosity mapping, and whole-exome sequencing. A homozygous mutation was identified disrupting a splice site in exon 5 of the DJ1 (PARK7) gene. Clinical details and a video are provided. DJ1 mutations are a rare cause of atypical complex parkinsonism. Exome sequencing is efficacious in identifying the causal gene variant.
RESUMO
We have established that the frequency of LRRK2 mutations in a series of 118 cases of familial Parkinson's disease is 5.1%. In the largest family with autosomal dominant, late-onset Parkinson's disease where affected subjects share a Y1699C missense mutation we provide a detailed clinical, pathological and imaging report. The phenotype in this large British kindred included asymmetrical, levodopa-responsive parkinsonism where unilateral leg tremor at onset and foot dystonia were prominent features. There was no significant abnormality of cognition but there was prominent behavioural disorder. We observed a lower age of onset in successive generations. Histopathology in one patient showed substantia nigra cell loss and Lewy body formation, with small numbers of cortical Lewy bodies. 18F-dopa positron emission tomography (PET) in another patient showed a pattern of nigrostriatal dysfunction typical of idiopathic Parkinson's disease. 18F-dopa-PET scans in unaffected family members prior to identifying the disease locus did not detect subclinical nigrostriatal dysfunction. Olfaction was assessed in affected subjects and Lewy bodies were identified in the olfactory bulb as well as cortex and brainstem of one deceased patient. In order to assess the role of mutations in this gene in other familial cases we undertook a mutation screen of all 51 exons of LRRK2 in 117 other smaller British kindreds with familial Parkinson's disease. The commonest mutation was G2019S and we also identified two novel mutations, R1941H and T2356I, in the coding sequence. These data suggest that parkinsonism caused by mutations in LRRK2 is likely to represent the commonest locus for autosomal dominant Parkinson's disease with a phenotype, pathology and in vivo imaging similar to idiopathic, late-onset Parkinson's disease.
Assuntos
Mutação de Sentido Incorreto , Doença de Parkinson/genética , Proteínas Serina-Treonina Quinases/genética , Adulto , Idade de Início , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Análise Mutacional de DNA , Inglaterra , Feminino , Genes Dominantes , Ligação Genética , Testes Genéticos , Haplótipos , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Escore Lod , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto/genética , Bulbo Olfatório/patologia , Doença de Parkinson/diagnóstico , Doença de Parkinson/patologia , Linhagem , Tomografia por Emissão de Pósitrons , Compostos RadiofarmacêuticosRESUMO
Analysis of the apolipoprotein E genotype in sibpairs with Parkinson's disease showed the E4 allele was over represented in those who shared the adjacent chromosome 19 markers. This suggests that apolipoprotein E4 is responsible for the linkage peak in this region and that it is a modest risk factor for Parkinson's disease.
Assuntos
Apolipoproteínas E/genética , Cromossomos Humanos Par 19/genética , Ligação Genética , Doença de Parkinson/genética , Alelos , Apolipoproteína E4 , Saúde da Família , Frequência do Gene , Genótipo , Humanos , Desequilíbrio de Ligação , Escore Lod , Repetições de Microssatélites , IrmãosRESUMO
Parkinson's disease (PD) is a genetically heterogeneous disease. Recently, significant linkage has been reported to a 39.5 cM region on the long arm of chromosome 2 (2q36-37; PARK11) in North American Parkinson families under an autosomal dominant model of inheritance. We have performed a replication study to confirm linkage to this region in a European population. Linkage analysis in 153 individuals from 45 European families with a strong family history of PD did not show any significant LOD score in this region. Therefore, PARK11 does not seem to play a major role for familial PD in the European population.
