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Aim: The aim of the present investigation is to study the epidemiology of Alport syndrome in southern Sweden, to search for mutations in the COL4A5 gene and to estimate the mutation frequency., Patients and Methods: Patients with suspected Alport syndrome were identified in an area with a population of 1.45 million. Clinical criteria were used to establish the diagnosis and samples for mutation analysis were collected. Mutation analyses were performed with Single-Stranded Conformation Polymorphism analysis (SSCP) of PCR-amplified genomic DNA., Results: Altogether 25 families with hereditary nephritis were identified. Alport syndrome with X-linked transmission was evident in 14 families, with juvenile (< 31 years) progression to end-stage renal failure (ESRF) in ten, and adult (> or = 31 years) in four families., Conclusion: The frequency of males with X-linked disease was calculated to one in 17,000 male births (95% confidence interval (CI) 1/10,500-1/28,600), and the prevalence to one in 40,000. A total of seven females with ESRF were identified, with a median age at ESRF of 45 years. The male to female ratio of cases with ESRF was 4.9 to 1. The risk of developing ESRF among females was from the expected incidence roughly estimated to 12%. Patients with X-linked disease constituted 1.8% of patients with ESRF in the examined area. A mutation was identified positive in 10 of 14 families with X-linked disease, but never in families not fulfilling the clinical criteria for Alport syndrome. In families with juvenile phenotype and positive mutation analysis, the mutation frequency was calculated to between 1/78,000 and 1/198,000 (95% CI 1/42,000-1/177,000) if the effective fertility was estimated to be between 0 and 0.2.

Background: Goodpasture's disease (GP) is a rare but severe disease characterized by anti-glomerular basement membrane antibodies, rapidly progressive glomerulonephritis and lung haemorrhage. The autoantibodies are restricted to a narrow epitope region on the NC1 domain of the alpha 3 chain of type IV collagen. GP is strongly associated with major histocompatibility complex (MHC) allele HLA DRB1-15. Recent research, however, has failed to identify a T-cell epitope with molecular characteristics that explain the relationship between the MHC class II molecule and the autoantibody generation. We hypothesized that an as yet unidentified sequence variant in exons 48-52 of the COL4A3 gene that encodes the NC1 domain of the type IV collagen alpha 3 chain could generate a new peptide sequence that, through interaction with specific MHC class II molecules, would increase the risk of developing GP., Methods: All patients previously treated for GP at the Lund and Malmö University Hospitals, who were alive at the time of the study, were asked to participate. DNA was extracted from leukocytes and subjected to genomic tissue typing and sequencing of the COL4A3 gene exons 48-52., Results: All 15 patients in the study had a nucleotide sequence in the COL4A3 gene encoding a protein identical to GenBank entry NM&#95;000091. HLA D allele distribution was in line with previous publications, showing a strong positive association between HLA DRB1-15, HLA DQB1-6 and GP (P<0.02). Of the 15 GP patients, 73% carried HLA DRB1-15 and 87% carried the HLA DQB1-6 antigen. Corresponding figures for the controls were 27 and 50%., Conclusion: This study effectively falsifies the hypothesis that a minor alteration in the COL4A3 gene could be a major factor in the aetiology of GP. Scandinavian GP patients have an MHC distribution similar to that which has been described previously for Anglo-Saxon patients.