Abstract
Alport syndrome is a hereditary glomerular nephritis associated with hearing loss and eye abnormalities and is classified as X-linked Alport syndrome, autosomal recessive Alport syndrome, and autosomal dominant Alport syndrome. Autosomal dominant Alport syndrome is caused by a mutation in the gene encoding type IV collagen α3 (α3[IV]); (COL4A3), or α4 (α4[IV]); (COL4A4). Autosomal dominant Alport syndrome progresses more gradually than male X-linked Alport syndrome and autosomal recessive Alport syndrome. Differentiating autosomal dominant Alport syndrome from thin basement membrane nephropathy, which shows better kidney prognosis, remains challenging. Because autosomal dominant Alport syndrome is linked to a heterozygous mutation, type IV collagen is produced by the wild-type allele, and all α(IV) chains are supposed to be normally expressed. In this study, the pathologic findings of a patient with Alport syndrome with a novel COL4A4 heterozygous nonsense mutation were investigated. We observed weaker staining of α5(IV) in the glomerular basement membrane and enhanced expressions of α2(IV), laminin, and fibronectin, which were assumed to be caused by compensatory mechanisms for lack of enough α3α4α5(IV) expression in the glomerular basement membrane. These findings may be useful not only for differentially diagnosing autosomal dominant Alport syndrome from thin basement membrane nephropathy, but also for determining the extent of progression and predicting kidney prognosis.