Collagen Type IV-Related Nephropathies in Portugal: Pathogenic COL4A5 Mutations and Clinical Characterization of 22 Families

Alport syndrome (AS) is caused by pathogenic mutations in the genes encoding α3, α4 or α5 chains of collagen IV (COL4A3/COL4A4/COL4A5), resulting in hematuria, chronic renal failure (CRF), sensorineural hearing loss (SNHL) and ocular abnormalities. Mutations in the X-linked COL4A5 gene have been identified in 85% of the families (XLAS). In this study, 22 of 60 probands (37%) of unrelated Portuguese families, with clinical diagnosis of AS and no evidence of autosomal inheritance, had pathogenic COL4A5 mutations detected by Sanger sequencing and/or multiplex-ligation probe amplification, of which 12 (57%) are novel. Males had more severe and earlier renal and extrarenal complications, but microscopic hematuria was a constant finding irrespective of gender. Nonsense and splice site mutations, as well as small and large deletions, were associated with younger age of onset of SNHL in males, and with higher risk of CRF and SNHL in females. Pathogenic COL4A3 or COL4A4 mutations were subsequently identified in more than half of the families without a pathogenic mutation in COL4A5. The lower than expected prevalence of XLAS in Portuguese families warrants the use of next-generation sequencing for simultaneous COL4A3/COL4A4/COL4A5 analysis, as first-tier approach to the genetic diagnosis of collagen type IV-related nephropathies.info:eu-repo/semantics/publishedVersio

Meaning of leprosy for people who have experienced treatment during the sulfonic and multidrug therapy periods

Objetivo:analizar los significados de la lepra para las personas que fueron tratadas en el período sulfónico y en el período de poliquimioterapia.Método:estudio de naturaleza cualitativa fundamentado en el abordaje histórico cultural de Vygotsky, el cual orientó la construcción y análisis de los datos. Fueron incluidos ocho entrevistados que ya tuvieron lepra y que realizaron tratamiento en el período sulfónico y de poliquimioterapia, siendo participantes del Movimiento de Reintegración de Personas Afectadas por la Lepra.Resultados:los significados fueron organizados en tres núcleos de significación: manchas en el cuerpo: alguna cosa está fuera de orden; ¿Lepra o enfermedad de Hansen?; y lepra a partir de la inserción en el Movimiento de Reintegración de Personas Afectadas por la Lepra. Conclusión: los significados de la lepra para las personas tratadas en los dos períodos apuntan para la construcción compleja de los mismos, indicando diferencias y semejanzas en los dos períodos. Los profesionales de la salud pueden contribuir para el cambio de significados, ya que estos son socialmente construidos y las transformaciones son continuas.Objetivo:analisar significados da hanseníase para as pessoas que foram tratadas no período sulfônico e no período da poliquimioterapia.Método:estudo de natureza qualitativa fundamentado na abordagem histórico-cultural de Vigotski, a qual orientou a construção e análise dos dados. Foram incluídos oito entrevistados que já tiveram hanseníase e que realizaram tratamento no período sulfônico e da poliquimioterapia, sendo participantes do Movimento de Reintegração das Pessoas Atingidas pela Hanseníase.Resultados:os significados foram organizados em três núcleos de significação: manchas no corpo: alguma coisa está fora de ordem; lepra ou hanseníase? e hanseníase a partir da inserção no Movimento de Reintegração das Pessoas Atingidas pela Hanseníase.Conclusão:os significados de hanseníase para pessoas tratadas nos dois períodos apontam para a construção complexa dos mesmos, indicando diferenças e semelhanças nos dois períodos. Os profissionais de saúde podem contribuir para a mudança de significados, pois esses são socialmente construídos e as transformações são contínuas.Objective: to analyze the meanings of leprosy for people treated during the sulfonic and multidrug therapy periods.Method: qualitative nature study based on the Vigotski's historical-cultural approach, which guided the production and analysis of data. It included eight respondents who have had leprosy and were submitted to sulfonic and multidrug therapy treatments. The participants are also members of the Movement for Reintegration of People Affected by Leprosy.Results: the meanings were organized into three meaning cores: spots on the body: something is out of order; leprosy or hanseniasis? and leprosy from the inclusion in the Movement for Reintegration of People Affected by Leprosy.Conclusion: the meanings of leprosy for people submitted to both regimens point to a complex construction thereof, indicating differences and similarities in both treatments. Health professionals may contribute to the change of the meanings, since these are socially constructed and the changes are continuous