The gene corresponding to the putative Goodpasture antigen is present in Alport's syndrome.
Alport's syndrome is a heterogeneous group of inherited abnormalities of basement membranes that may result in progressive renal failure, defective hearing and lens abnormalities. The glomerular basement membrane (GBM) characteristically has areas of reduplication, lamellation and attenuation on electron microscopic examination. In the majority of affected males and some females, there is reduced or variable binding of serum from patients with anti-GBM disease (Goodpasture's syndrome) to these basement membranes. These sera contain antibodies directed against the Goodpasture antigen which has been thought to be located in the non-collagenous domain of the alpha3 chain of type IV collagen and is presumed to be important in cross-linking of the collagen molecules. The reduced staining for the Goodpasture antigen suggests that this structure is either absent or masked in Alport's syndrome. We have tested DNA from six unrelated individuals with Alport's syndrome. All had been transplanted for renal failure. The diagnosis of Alport's syndrome was made on the characteristic electron microscopic appearance of the renal basement membranes (n = 4), the presence of sensori-neural deafness (n = 4), a family history of Alport's syndrome (n = 5) and the presence of circulating inhibitable anti-GBM antibody activity post-transplant (n = 2). Oligonucleotides (20mers) corresponding to the 5' and 3' ends of the known 25 amino acid sequence for the putative Goodpasture antigen were used as primers for amplification of genomic DNA. The products were then blotted and probed with an intermediate 19-mer DNA. All Alport's patients contained a 75-bp fragment corresponding to the published peptide sequence for the non-collagenous domain of the alpha 3 chain of type IV collagen, suggesting that a large deletion of this region, the putative Goodpasture antigen, is unlikely to account for the defect in Alport's syndrome.
Savige
J A
JA
Department of Haematology, Repatriation General Hospital, Heidelberg, Victoria, Australia.
D000595:Amino Acid Sequence; D001324:Autoantigens / Q000235:genetics*; D001483:Base Sequence; D003094:Collagen / Q000235:genetics*; D024141:Collagen Type IV; D004247:DNA; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009394:Nephritis, Hereditary / Q000235:genetics* / Q000276:immunology; D016133:Polymerase Chain Reaction; D014960:X Chromosome
D001324:Autoantigens; D024141:Collagen Type IV; C057112:type IV collagen alpha3 chain; D003094:Collagen; D004247:DNA