Matsukura H, Higuchi A, Ieki A, Miyawaki T
Department of Pediatrics, Saiseikai Toyama Hospital, Japan.
Clin Nephrol. 2004 Oct;62(4):313-8. doi: 10.5414/cnp62313.
Alport syndrome is a genetically heterogeneous disorder, but most patients showed the X-linked form resulting from mutations in the COL4A5 gene. A few cases of mosaicism in Alport syndrome have been reported.
We describe the case of an 8-year-old boy with mosaicism in Alport syndrome. Punch skin biopsies were obtained from the patient's mother and monozygotic twin brother. Five biopsy specimens from non-Alport patients were used as controls. Immunohistochemical analysis was performed using rat monoclonal antibodies towards individual collagen IV(NC) domains.
Kidney tissue of the patient showed: mosaic expression of alpha3(IV), alpha4(IV) and alpha5(IV) in the glomerular basement membrane (GBM), distal tubular basement membrane (TBM) and Bowman's capsule; mosaic alpha6(IV) expression in the Bowman's capsule and distal TBM; and well-preserved expression of alpha1(IV) and alpha2(IV). The patient's skin exhibited mosaic alpha5(IV) expression. His mother and monozygotic twin brother disclosed a normal linear staining of alpha5(IV) in their epidermal basement membranes. This unusual mosaicism of alpha3(IV), alpha4(IV), alpha5(IV) and alpha6(IV) is consistent with a pattern of female heterozygotes of Alport syndrome.
This discordant phenotypic expression of Alport syndrome in monozygotic twins with unaffected parents suggests possible somatic mosaicism in the COL4A5 gene.
奥尔波特综合征是一种基因异质性疾病，但大多数患者表现为X连锁型，由COL4A5基因突变所致。已有少数奥尔波特综合征嵌合体病例的报道。
我们描述了一名患有奥尔波特综合征嵌合体的8岁男孩的病例。从患者的母亲和同卵双胞胎兄弟身上获取了皮肤打孔活检样本。将5例非奥尔波特综合征患者的活检标本用作对照。使用针对单个IV型胶原（NC）结构域的大鼠单克隆抗体进行免疫组织化学分析。
患者的肾组织显示：α3（IV）、α4（IV）和α5（IV）在肾小球基底膜（GBM）、远端肾小管基底膜（TBM）和鲍曼囊中有嵌合表达；α6（IV）在鲍曼囊和远端TBM中有嵌合表达；α1（IV）和α2（IV）表达保存完好。患者的皮肤表现出α5（IV）的嵌合表达。他的母亲和同卵双胞胎兄弟在其表皮基底膜中显示α5（IV）呈正常线性染色。α3（IV）、α4（IV）、α5（IV）和α6（IV）这种不寻常的嵌合现象与奥尔波特综合征女性杂合子的模式一致。
在父母未受影响的同卵双胞胎中，奥尔波特综合征这种不一致的表型表达提示COL4A5基因可能存在体细胞嵌合现象。
