IDENTIFICATION OF MUTATIONS IN THE COL4A5 COLLAGEN GENE IN ALPORT SYNDROME
IDENTIFICATION OF MUTATIONS IN THE COL4A5 COLLAGEN GENE IN ALPORT SYNDROME
复制标题
DOI：
10.1126/science.2349482
复制
发表时间：
1990-06-08
期刊：
影响因子：
56.9
通讯作者：
TRYGGVASON, K
中科院分区：
文献类型：
--
作者：
BARKER, DF;HOSTIKKA, SL;TRYGGVASON, K
X连锁Alport综合征是一种遗传性肾小球肾炎，其中肾功能的进行性丧失通常伴有听力的进行性丧失。Alport综合征患者肾小球基底膜（GBM）的超微结构缺陷暗示结构蛋白改变是肾炎的原因。COL4A5的产物，即α 5（IV）胶原蛋白链，是肾内GBM的特异性组分，并且该基因与Alport综合征一样定位于相同的X染色体区域。在犹他州的3例Alport综合征患者中发现了COL4A5的3种结构畸变，一种基因内缺失，一种Pst I位点变异，以及一种未表征的异常，这3种结构畸变似乎可引起肾炎和耳聋，具有等位基因特异性严重程度。
X-linked Alport syndrome is a hereditary glomerulonephritis in which progressive loss of kidney function is often accompanied by progressive loss of hearing. Ultrastructural defects in glomerular basement membranes (GBM) of Alport syndrome patients implicate an altered structural protein as the cause of nephritis. The product of COL4A5, the .alpha.5(IV) collagen chain, is a specific component of GBM within the kidney, and the gene maps to the same X chromosomal region as does Alport syndrome. Three structural aberrations were found in COL4A5, an intragenic deletion, a Pst I site variant, and an uncharacterized abnormality, which appear to cause nephritis and deafness, with allele-specific severity, in three Alport syndrome kindreds in Utah.