Autosomal recessive Alport syndrome: immunohistochemical study of type IV collagen chain distribution.
Alport syndrome (AS) is an hereditary disease of basement membrane collagen. It is mainly transmitted as a dominant X-linked trait and caused by mutations in the COL4A5 gene encoding the alpha 5 chain of type IV collagen. However, autosomal recessive AS due to mutations in the COL4A3 or COL4A4 genes could represent up to 15% of AS. Using the immunofluorescence technique, we analyzed the distribution of the different chains of type IV collagen in renal (12 specimens) and skin (4 specimens) basement membranes of 12 AS patients belonging to 11 unrelated kindreds in which autosomal recessive inheritance had been demonstrated (3 kindreds) or was suggested by clinical and genealogic data (8 kindreds). The renal and skin distribution was normal in one patient with COL4A4 mutations. A peculiar pattern of distribution of the alpha 3-alpha 5(IV) chains was observed in the other patients. It was characterized the co-absence of the alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains in the glomerular basement membrane, and the presence of the alpha 5(IV) chain in a series of extraglomerular basement membranes including capsular, collecting ducts and epidermal basement membranes, a combination never observed in X-linked AS. This immunohistochemical pattern is correlated with the specific distribution of the alpha 3-alpha 5 chains of type IV collagen chains within extraglomerular basement membranes. It could be a useful marker for the identification of autosomal recessive AS.
Gubler
M C
MC
Département de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades et Université René Descartes-Paris V, France.
Knebelmann
B
B
Beziau
A
A
Broyer
M
M
Pirson
Y
Y
Haddoum
F
F
Kleppel
M M
MM
Antignac
C
C
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D001485:Basement Membrane / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D002648:Child; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D005192:Family Health; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009154:Mutation; D009394:Nephritis, Hereditary / Q000235:genetics / Q000378:metabolism*; D010375:Pedigree; D012867:Skin / Q000378:metabolism* / Q000473:pathology
D000911:Antibodies, Monoclonal; D003094:Collagen