Gubler M C, Knebelmann B, Beziau A, Broyer M, Pirson Y, Haddoum F, Kleppel M M, Antignac C
Département de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades et Université René Descartes-Paris V, France.
Kidney Int. 1995 Apr;47(4):1142-7. doi: 10.1038/ki.1995.163.
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.
阿尔波特综合征（AS）是一种基底膜胶原蛋白的遗传性疾病。它主要以X连锁显性性状遗传，由编码IV型胶原α5链的COL4A5基因突变引起。然而，由于COL4A3或COL4A4基因突变导致的常染色体隐性AS可能占AS的15%。我们采用免疫荧光技术，分析了12例AS患者肾（12个标本）和皮肤（4个标本）基底膜中IV型胶原不同链的分布情况。这12例患者来自11个无亲缘关系的家族，其中3个家族已证实为常染色体隐性遗传，8个家族根据临床和系谱数据提示为常染色体隐性遗传。1例COL4A4基因突变患者的肾和皮肤分布正常。在其他患者中观察到α3 - α5（IV）链的一种特殊分布模式。其特征是肾小球基底膜中α3（IV）、α4（IV）和α5（IV）链共同缺失，而在一系列肾球外基底膜（包括包膜、集合管和表皮基底膜）中存在α5（IV）链，这种组合在X连锁AS中从未观察到。这种免疫组化模式与IV型胶原α3 - α5链在肾球外基底膜中的特定分布相关。它可能是鉴定常染色体隐性AS的一个有用标志物。
