Siblings with Alport’s syndrome showing unique staining patterns for α5(IV) and α6(IV) chains of collagen type IV

Abstract

Here we report two brothers with electron-microscopically diagnosed Alport's syndrome (AS) who showed normal staining patterns for the alpha1(IV)-alpha4(IV) chains of collagen type IV, but abnormal expression of the alpha5(IV) and alpha6(IV) chains. Both patients had microscopic hematuria and mild proteinuria from around 10 years old, and had renal biopsies at 23 (older) and 26 (younger) years old due to increased proteinuria (0.5-0.8 g/day) with normal renal function. A skin biopsy of the patients' mother showed similar abnormal staining patterns for the alpha5(IV) and alpha6(IV) chains in the skin basement membranes. Both of them showed slow progression of renal dysfunction and no extrarenal manifestations. The existences of incomplete alpha3,alpha4,alpha5(IV) molecules in the glomerular basement membrane (GBM) and inadequately formed alpha5,alpha5,alpha6(IV) molecules are suggested for these patients. A missense mutation of the COL4A5 gene may present in this family as possible X-linked inheritance and a mild form of AS.