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P. S. Bernstein, F. Ahmed, M. Gregory; Retinal Pathology Linked to Nephropathy in Alport Syndrome. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1395.
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Many inherited systemic diseases are associated with varying degrees of corneal, lens, and retinal degeneration. Alport syndrome is characterized by a juvenile onset of hematuria followed by changes in glomerular basement membranes (GBM). The hallmark of glomerular changes in Alport syndrome is irregular thickening, thinning, and splitting of the GBM. X-linked Alport syndrome is caused by mutations in the COL4A5 gene. The rarer autosomal recessive form is due to mutations in other basement membrane collagen genes: COL4A3 or COL4A4. Alport syndrome’s best known ocular manifestation is anterior lenticonus, but retinal pathology is increasingly recognized as well, especially since retinal pigment epithelial basement membrane and GBM are structurally similar.
Subjects had complete eye examinations and retinal imaging using autofluorescence, fundus photography, and optical coherence tomography (OCT). Blood samples were collected for genotyping of COL4A5 mutations.
21 subjects (11 female and 10 male) patients have currently enrolled in this ongoing study. Genetic analyses showed 96% of study patients have a mutation associated with the COL4A5 gene. Of these patients, the 10 expressing L1649R and C1654S mutations had no retinal pathology with the exception for one patient with vitreomacular traction syndrome. Patients with other COL4A5 mutations: G576S, G96A, G1060X, Lys1097ter, 3528+T, del ex2 had significant retinal pathology. Retinal pathology included peri-macular flecks, pigmentary changes, and reduced temporal OCT thickness.
The L1649R and C1564S mutations in the COL4A5 gene, which cause a relatively mild form of Alport syndrome characterized by late onset renal failure, were not associated with substantial retinal pathology. Other COL4A5 mutations associated with more significant renal pathology exhibited numerous retinal abnormalities including reduced temporal retina thickness and pigmentary changes. There was strong concordance of retinal phenotypes between Alport siblings. The pathological basis for Alport syndrome’s retinal abnormalities remains to be explored.
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