Linkage of a gene causing familial focal segmental glomerulosclerosis to chromosome 11 and further evidence of genetic heterogeneity

Focal segmental glomerulosclerosis (FSGS) is a pathological entity characte rized by proteinuria, nephrotic syndrome, and the progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD), Recently , familial forms of FSGS have been identified. Two families with autosomal dominant FSGS were evaluated for linkage using 351 genomic microsatellite m arkers. Linkage, multipoint analysis, and tests for heterogeneity were perf ormed on the subsequent results. In addition, three small families were use d for haplotype analysis. Evidence for linkage was found on chromosome 11q2 1-q22 for the largest family, with a maximum lod score of 9.89. The gene is currently localized to an 18-cM area between flanking markers D11S2002 and D11S1986. The disease in a second family was not linked to this locus or t o a previously described locus on chromosome 19q13. There were no shared ha plotypes among affected individuals in the three smaller families. Our find ings demonstrate that genetic heterogeneity is prevalent in FSGS in that at least three genes cause the FSGS phenotype. Identification of the genes th at cause familial FSGS will provide valuable insights into the molecular ba sis and pathophysiology of FSGS. (C) 1999 Academic Press.