Synopsis Recent studies have suggested that expanded CAG/CTG repeats contribute to the genetic aetiology of schizophrenia and bipolar disorder. However, the nature of this contribution is uncertain and difficult to predict from other known trinucleotide repeat diseases that display much simpler patterns of inheritance. We have sought to replicate and extend earlier findings using Repeat Expansion Detection in an enlarged sample of 152 patients with schizophrenia, 143 patients with bipolar disorder, and 160 controls. We have also examined DNA from the parents of 62 probands with schizophrenia or bipolar disorder. Our results confirm our earlier, preliminary findings of an association between expanded trinucleotide repeats and both schizophrenia and bipolar disorder. However, our data do not support the hypothesis that trinucleotide repeat expansion can alone explain the complex patterns of inheritance of the functional psychoses neither can this mechanism fully explain apparent anticipation.
Abstract As part of an extensive study in the Portuguese Island population of families with multiple patients suffering from bipolar disorder and schizophrenia, we performed an initial genome‐wide scan of 16 extended families with bipolar disorder that identified three regions on chromosomes 2, 11, and 19 with genome‐wide suggestive linkage and several other regions, including chromosome 6q, also approached suggestive levels of significance. Dick et al. [2003: Am J Hum Genet 73:107–114] recently reported in a study of 250 families with bipolar disorder a maxLOD score of 3.61 near marker D6S1021 on chromosome 6q. This study replicates this finding having detected a peak NPL = 2.02 ( P = 0.025) with the same marker D6S1021(104.7 Mb). Higher‐density mapping provided additional support for loci on chromosome 6 including marker D6S1021 with an NPL = 2.59 ( P = 0.0068) and peaking at marker D6S1639 (125 Mb) with an NPL = 3.06 ( P = 0.0019). A similar pattern was detected with higher‐density mapping of chromosome 11 with an NPL = 3.15 ( P = 0.0014) at marker D11S1883 (63.1 Mb). Simulations at the density of our fine mapping data indicate that less than 1 scan out of 10 would find two such scores genome‐wide in the same scan by chance. Our findings provide additional support for a susceptibility locus for bipolar disorder on 6q, as well as, suggesting the importance of denser scans. Published 2004 Wiley‐Liss, Inc.
The Operational Criteria Checklist (OPCRIT) generates diagnoses according to 12 operational diagnostic systems (e.g. DSM-III, DSM-III-R, Research Diagnostic Criteria, ICD-10).To examine the agreement between diagnoses generated by the OPCRIT, as completed by the interviewer, with a best-estimate lifetime procedure using the OPCRIT.Subjects came from large multi-generational bipolar or schizophrenia pedigrees (n = 100), and from a sample of unrelated subjects with schizophrenia (n = 40). We analysed the diagnostic agreement between OPCRIT diagnoses generated by the interviewer and our best-estimate OPCRIT diagnoses, according to DSM-III-R and ICD-10, using Cohen kappa statistics.Excellent agreement was found between interviewer OPCRIT diagnoses and OPCRIT diagnoses made by the best-estimate lifetime consensus procedure for DSM-III-R (kappa = 0.83) and ICD-10 (kappa = 0.81).Results suggest that this procedure for diagnostic assessment is an efficient alternative to classic best-estimate diagnosis procedures.
Este estudo tem por objetivo investigar na literatura selecionada quais são as principais alterações oftalmológicas relacionadas à Doença de Stargardt. Para este fim, foi realizada uma revisão integrativa de literatura que utilizou artigos publicados nas principais bases de dados nos últimos vinte anos, além de livros da oftalmologia. Os resultados indicam que a Doença de Stargardt causa perda da visão central, discromatopsia, fotofobia e escotomas centrais devido ao depósito de lipofuscina no epitélio pigmentar da retina (EPR) e fotorreceptores da mácula. A fundoscopia mostra atrofia macular com manchas branco-amareladas. Estágios iniciais apresentam alterações maculares e escotomas centrais, progredindo para atrofia extensa do EPR e coriocapilar. Não há tratamento específico, mas abordagens em desenvolvimento incluem suplementação vitamínica, terapias de reposição proteica e celular, edição genética e dispositivos visuais. A doença impacta significativamente a qualidade de vida dos pacientes. Em conclusão, as principais alterações são: perda da visão central, discromatopsia, fotofobia, escotomas centrais, atrofia macular, depósitos de lipofuscina e alterações no eletrorretinograma.
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