PDF(Pubmed)
Abstract：
Alport syndrome has been linked to three different genes, that is, COL4A3, COL4A4 and COL4A5. It is characterized by progressive and non-specific glomerulosclerosis with irregular thickening of the glomerular basement membrane (GBM). At times, the histopathologic picture is dominated by lesions that are consistent with focal and segmental glomerulosclerosis or IgA nephropathy. Here, we report the cases of two related individuals (mother and son) who were diagnosed with COL4A5-related Alport syndrome due to a missense variant (p.Gly1170Ser) in a G-X-Y repeat and found to present the same highly unusual histopathological abnormalities on their kidney biopsies. One of the abnormalities shared, which does not appear to have been reported, was reduced COL4A5 immunolabeling that was limited to Bowman\'s capsule even though the ultrastructure of the GBM was distorted. The other abnormality was superimposed segmental IgA deposition in both individuals, accompanied by mesangial changes in the mother. We feel that these findings provide novel insight into the mechanisms of disease manifestation in Alport syndrome. They suggest, in particular, that collagen expression and/or assemblies in Bowman\'s capsule is more vulnerable to missense mutations in COL4A5 than elsewhere in the kidney. Our findings also suggest that certain coinherited gene polymorphisms act as unexpectedly important phenotypic determinants in COL4A-related disorders.
摘要：
Alport综合征与三个不同的基因有关,也就是说,COL4A3、COL4A4和COL4A5。它的特征是进行性和非特异性肾小球硬化，肾小球基底膜（GBM）不规则增厚。有时,组织病理学特征主要是与局灶性和节段性肾小球硬化或IgA肾病一致的病变。这里,我们报告了两名相关个体（母亲和儿子）的病例，这些个体由于错义变异而被诊断为COL4A5相关的Alport综合征（p.Gly1170Ser）在G-X-Y重复序列中，发现其肾脏活检显示出相同的高度异常的组织病理学异常。共有的异常之一，似乎没有报道，即使GBM的超微结构变形，也减少了COL4A5的免疫标记，这仅限于Bowman的胶囊。另一个异常是两个个体的节段性IgA沉积叠加，伴随着母亲的系膜变化。我们认为这些发现为Alport综合征的疾病表现机制提供了新的见解。他们建议,特别是,与肾脏其他部位相比，鲍曼胶囊中的胶原蛋白表达和/或组装更容易受到COL4A5错义突变的影响。我们的发现还表明，某些共遗传的基因多态性在COL4A相关疾病中具有出乎意料的重要表型决定因素。
