Genotype- phenotype correlation in Alport syndrome and benign familial hematuria: proposal of a new concept of type IV collagen associated nephropathies

Abstract

 Alport syndrome (AS) and benign familial hematuria (BFH) are both familial inherited nephropathies. Gene mutations in COL4A5 located on Xq22 are believed to be causative in most patients with AS, while homozygote or compound heterozygote mutations and heterozygote mutations in COL4A3 gene or COL4A4 gene located on chromosome 2 are known to be associated with autosomal recessive AS and BFH, respectively.
 Accumulated knowledge, however, in regard to genotype- phenotype correlation has revealed that there is no one-to-one correspondence between genetic mutations and clinical pictures as in other gene mutaions. We experienced a family with BFH caused by COL4A5 mutation suggesting that COL4A5 should be added to the list of causative genes for BFH, and, we therefore propose a new concept of “type IV collagen associated nephropathies” which involve both AS and BFH diagnosed by clinical findings and can be used for diseases caused by abnormal configuration of glomerular basement membrane due to mutations in COL4A3, COL4A4 and COL4A5.