BACKGROUND: Alport syndrome is an inherited disorder affecting the kidney, eye and ear arising from mutations in the gene COL4A5, which encodes the α5 chain of type IV collagen. Structural defects of glomerular basement membranes in Alport syndrome are associated in most instances with failure to detect the α3, α4, and α5 chains of type IV collagen as well as the Alport antigen that is identified in normal tissues by a genetically discriminating alloantibody and monoclonal antibody. Anterior lenticonus is an ocular abnormality pathognomonic of Alport syndrome that is associated with marked thinning of the anterior lens capsule (ALC). The reactivity of Alport ALC with type IV collagen antibodies has not previously been reported. EXPERIMENTAL DESIGN: ALCs were obtained at the time of cataract extraction from two unrelated males with Alport syndrome and anterior lenticonus, and stained with antibodies against the α1, α2, α3 and α4 chains of type IV collagen, as well as an antibody against the α5(IV) chain. Controls consisted of ALCs from a normal individual and from a patient with diabetes mellitus. RESULTS: Normal and diabetic ALCs reacted with antibodies against the α1, α2, α3, and α4 chains of type IV collagen and the α5(IV) chain. In one of the Alport patients, ALC showed no reactivity with antibodies against the α5(IV) chain and the α3 and α4 chains of type IV collagen. In the second patient, ALC reactivity with these antibodies was preserved. Epidermal basement membranes from this second patient also showed reactivity with antibody against the α5(IV) chain, unlike most males with Alport syndrome. In both Alport patients, ALCs reacted with antibodies against the α1(IV) and α2(IV) chains. CONCLUSIONS: These findings suggest that anterior lenticonus in patients with Alport syndrome may be associated with absence of the α3 and α4 chains of type IV collagen, as well as the α5(IV) chain, from anterior lens capsule. On the other hand, these chains may be present in Alport patients with anterior lenticonus. The precise structural basis for mechanical weakness of the anterior lens capsule in patients with Alport syndrome remains to be determined.
|Original language||English (US)|
|Number of pages||5|
|State||Published - 1994|
- Anterior lenticonus