RESUMO
BACKGROUND: Alport syndrome is a genetically heterogeneous disorder, but most patients showed the X-linked form resulting from mutations in the COL4A5 gene. A few cases of mosaicism in Alport syndrome have been reported. METHODS: We describe the case of an 8-year-old boy with mosaicism in Alport syndrome. Punch skin biopsies were obtained from the patient's mother and monozygotic twin brother. Five biopsy specimens from non-Alport patients were used as controls. Immunohistochemical analysis was performed using rat monoclonal antibodies towards individual collagen IV(NC) domains. RESULTS: Kidney tissue of the patient showed: mosaic expression of alpha3(IV), alpha4(IV) and alpha5(IV) in the glomerular basement membrane (GBM), distal tubular basement membrane (TBM) and Bowman's capsule; mosaic alpha6(IV) expression in the Bowman's capsule and distal TBM; and well-preserved expression of alpha1(IV) and alpha2(IV). The patient's skin exhibited mosaic alpha5(IV) expression. His mother and monozygotic twin brother disclosed a normal linear staining of alpha5(IV) in their epidermal basement membranes. This unusual mosaicism of alpha3(IV), alpha4(IV), alpha5(IV) and alpha6(IV) is consistent with a pattern of female heterozygotes of Alport syndrome. CONCLUSION: This discordant phenotypic expression of Alport syndrome in monozygotic twins with unaffected parents suggests possible somatic mosaicism in the COL4A5 gene.
Assuntos
Colágeno Tipo IV/metabolismo , Mosaicismo , Nefrite Hereditária/genética , Fenótipo , Gêmeos Monozigóticos , Criança , Colágeno Tipo IV/genética , Regulação da Expressão Gênica , Humanos , Rim/patologia , Masculino , Nefrite Hereditária/metabolismoRESUMO
The relationship between the titer of pemphigus antibody and the clinical course of the disease was investigated in 15 patients with various types of pemphigus. Although antibody titers generally ran parallel to fluctuations of the clinical course, the elevation of antibody titer appeared to follow the re-appearance or exacerbation of the lesions on 10 occasions in 6 patients, while it appeared to precede the latter only on 2 occasions in 2 patients. In addition, the disappearance of the antibody was considerably delayed after disappearance of skin lesions in 2 cases. These findings suggest that the pemphigus antibody is the result of skin damage, rather than the cause of pemphigus itself.