RESUMO
OBJECTIVES: Diagnosis of Wilson disease (WD) is difficult and, as early detection may prevent all symptoms, it is essential to know the exact prevalence to evaluate the cost-efficacy of a screening program. As the number of WD patients was high in our population, we wished to estimate prevalence by determining the carrier frequency for clinically relevant ATP7B mutations. METHODS: To estimate prevalence, screening for the most prevalent mutation was performed in 1661 individuals with ancestry in Gran Canaria, and the frequency of other mutations was estimated from patient records. Alternatively, ATP7B mutations were detected from exomes and genomes from 851 individuals with Canarian ancestry, 236 from Gran Canaria, and a public Spanish exome database. RESULTS: Estimated carrier frequencies in Gran Canaria ranged from 1 in 20 to 28, depending on the method used, resulting in prevalences of 1 case per 1547 to 3140 inhabitants. Alternatively, the estimated affected frequencies were 1 in 5985 to 7980 and 1 in 6278 to 16,510 in the archipelago or mainland Spain respectively. CONCLUSIONS: The number of carriers predicts much higher prevalences than reported, suggesting that WD is underdiagnosed; specific mutations may remain unnoticed due to low penetrance or no signs of disease at all; regional prevalence rather than national prevalence should be considered in cost-efficacy models to approach preventive screening in the asymptomatic population and genetic screening strategies will have to deal with the genetic heterogeneity of ATP7B in the general population and in patients.
Assuntos
Degeneração Hepatolenticular , ATPases Transportadoras de Cobre/genética , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/epidemiologia , Degeneração Hepatolenticular/genética , Humanos , Mutação , Sistema de Registros , EspanhaRESUMO
We report a case of chronic myeloid leukemia in chronic stage with 48 chromosomes and four BCR/ABL1 fusion signals on two out of three chromosomes 9 and two signals on the two Philadelphia chromosomes. These abnormalities were detected by both conventional cytogenetic analysis and metaphase and interphase fluorescence in situ hybridization studies in approximately 90% of the cells at diagnosis. Real-time-polymerase chain reaction studies on peripheral blood showed b3a2(p210) and e1a2(p190) BCR/ABL1 fusion transcripts. During treatment with imatinib, the patient was asymptomatic with hematological remission. Cytogenetic and fluorescence in situ hybridization analysis revealed that only 6.6% of cells had the initial majority line karyotype, with disappearance of the p210 but increased p190 transcript, which led to the treatment being changed. We discuss the implication of cytogenetic and molecular alterations in the patient's evolution and treatment.
Assuntos
Proteínas de Fusão bcr-abl/genética , Leucemia Mieloide de Fase Crônica/genética , Adulto , Análise Citogenética , Humanos , Hibridização in Situ Fluorescente , Masculino , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Aportamos el primer caso acerca de hidranencefalia, a la literatura médica dominicana y otro a la literatura médica mundial. Spielmeyer, en 1905, fue quien aparentemente introdujo el término de "hidranencefalia". Nuestro caso presentó signos de cianosis y dificultad respiratoria. La irritabilidad y las convulsiones son frecuentes en el período neonatal, asociado a malformaciones es raro y los niños pueden estar bien formados antes de que se reconozca el defecto cerebral. Los hemisferios cerebrales están casi completamente ausentes
