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.