Hereditary nephritis (HN) is associated with antigenically abnormal glomerular basement membrane (GBM) manifest by reduced or absent binding of MCA-P1, a mouse monoclonal antibody which recognizes Goodpasture antigen.
Hereditary nephritis (HN) is associated with antigenically abnormal glomerular basement membrane (GBM) manifest by reduced or absent binding of MCA-P1, a mouse monoclonal antibody which recognizes Goodpasture antigen.
Pooled normal collagenase-solubilized GBM (CS-GBM) and CS-GBM from three patients with either end-stage renal failure (ESK1-3) or HN (HNK1-3), were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis gel and, after transfer by Western blotting to nitrocellulose, reacted with sera from six patients with anti-GBM disease (GPS1-6) or anti-GBM antibody containing sera from three transplanted HN patients (HNS1-3), different from those patients with HN contributing HNK1-3.
The product of COL4A5, the alpha 5(IV) collagen chain, is a specific component of GBM within the kidney, and the gene maps to the same X chromosomal region as does Alport syndrome.
To determine whether the alpha 3(IV) gene (COL4A3) may be mutated in Alport syndrome, we localized it, by somatic cell hybrid analysis and in situ hybridization of metaphase chromosomes, to chromosome 2q35-2q37.
Studies with sera from patients with Goodpasture's syndrome, or monoclonal antibodies specific for the Goodpasture antigen, show that the Goodpasture antigenis absent or masked in the kidneys of individuals with Alport's syndrome.
The location of the COL4A5 gene, which has recently been shown to be mutated in at least some families with Alport syndrome, was determined with respect to the same physical breakpoints.
Among patients with Alport's syndrome, five (45%) had elevated titres of thyroid microsomal antibodies and eight (73%) had positive titres of thyroglobulin antibodies, whereas only one healthy relative (6%) had circulating antithyroid antibodies.
To identify COL4A5 mutations in patients from Germany with clinically defined AS, DNA from 20 unrelated patients was analyzed by conventional Southern blotting.
These results also suggest that leiomyomatosis might be due to the alteration of a second gene involved in smooth muscle cell proliferation, which is located upstream of the COL4A5 gene, and that there might be a contiguous gene deletion syndrome, involving at least the genes coding for congenital cataract, DL and AS.
Mutations in the COL4A5 collagen gene have been implicated as the primary defect in Alport syndrome, a heritable disorder characterized by sensorineural deafness and glomerulonephritis that progresses to end-stage renal failure.
DNA rearrangements in the alpha 5(IV) collagen gene (COL4A5) of individuals with Alport syndrome: further refinement using pulsed-field gel electrophoresis.
In earlier studies, intragenic deletions of COL4A5 were detected in a subset of patients with Alport syndrome (AS), a hereditary defect of basement membranes.