Mutations in theCOL4A4andCOL4A3Genes Cause Familial Benign Hematuria

Abstract

ABSTRACT. Familial benign hematuria (FBH) is a common autosomal dominant disorder characterized by the presence of persistent or recurrent hematuria. The clinical and pathologic features of this syndrome resemble those of early Alport syndrome (AS), and for this reason a common molecular defect has been proposed. TheCOL4A3/4genes seem to be involved in both autosomal AS and FBH. This study involves a linkage analysis for theCOL4A3/4loci and a search for mutations within these genes in 11 biopsy-proven FBH families. Haplotype analysis showed that linkage to theCOL4A3/4locus could not be excluded in eight of nine families. One family was not linked to this locus; however, it included three affected women who could be X-linked AS carriers. Two families were too small to perform linkage analysis.COL4A3andCOL4A4mutation screening disclosed six new pathogenic mutations, two in theCOL4A3gene (G985V and G1015E) and four in theCOL4A4gene (3222insA, IVS23-1G>C, 31del11, and G960R). It is the first time that mutations within theCOL4A3gene are described in families with FBH. This study clearly demonstrates the main role of theCOL4A4andCOL4A3genes in the pathogenesis of FBH.