Alport syndrome and thin glomerular basement membrane disease.
Alport syndrome and thin glomerular basement membrane disease.
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DOI：
10.1681/asn.v991736
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发表时间：
1998-09
期刊：
影响因子：
--
通讯作者：
C. Kashtan
中科院分区：
文献类型：
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作者：
C. Kashtan
Alport综合征（AS）是一种全身性遗传性基底膜疾病，临床表现为血尿、进行性肾炎伴蛋白尿和肾功能下降、感音神经性耳聋和眼部异常。AS的自然史是性别依赖性的：受影响的男性通常患有严重的疾病，而女性的AS病程往往是温和的。古特里（1）于1902年首次描述了家族性血尿。Hurst（2）和Alport（3）对该家族的随访研究描述了肾病的进行性、与耳聋的相关性以及受影响男性的预后较差。20世纪70年代早期，几个研究小组进行的电子显微镜研究确定肾小球基底膜（GBM）是AS原发性肾脏异常的部位（4-6）。1980年至1990年的一系列报道将AS确定为IV型胶原的遗传性疾病：免疫组织学研究揭示了AS基底膜的异常IV型胶原组成（7，8）; Alport基因座定位于X染色体（9）;克隆新的IV型胶原基因（COL 4A 5）并将其分配到与Alport基因座相同的X染色体区域（10）;以及，最后，鉴定X连锁AS患者中的第一COL 4AS突变（11）。
Alport syndrome (AS) is a generalized inherited disorder of basement membranes, manifested by hematuria, progressive nephritis with proteinuria and declining renal function, sensorineural deafness, and ocular abnormalities. The natural history of AS is gender-dependent: affected males typically have severe disease, while the course of AS in females tends to be mild. The first description of familial hematuria was provided by Guthrie (1) in 1902. Follow-up studies of this family by Hurst (2) and Alport (3) described the progressive nature of the nephropathy, its association with deafness, and the poorer prognosis in affected males. Electron microscopic investigations carried out by several groups in the early 1970s identified the glomerular basement membrane (GBM) as the site of the primary renal abnormality in AS (4-6). A series of reports between 1980 and 1990 established AS as an inherited disease of type IV collagen: immunohistologic studies revealing abnormal type IV collagen composition of AS basement membranes (7,8); mapping of an Alport locus to the X chromosome (9); cloning of a new type IV collagen gene (COL4A5) and its assignment to the same region of the X chromosome as the Alport locus (10); and, finally, identification of the first COL4AS mutations in patients with X-linked AS ( 1 1).