Segal Y, Peissel B, Renieri A, de Marchi M, Ballabio A, Pei Y, Zhou J
Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Am J Hum Genet. 1999 Jan;64(1):62-9. doi: 10.1086/302213.
Deletions encompassing the 5' termini of the paired type IV collagen genes COL4A5 and COL4A6 on chromosome Xq22 give rise to Alport syndrome (AS) and associated diffuse leiomyomatosis (DL), a syndrome of disseminated smooth-muscle tumors involving the esophagus, large airways, and female reproductive tract. In this study, we report isolation and characterization of two deletion junctions. The first, in a patient described elsewhere, arose by a nonhomologous recombination event fusing a LINE-1 (L1) repetitive element in intron 1 of COL4A5 to intron 2 of COL4A6, resulting in a 13.4-kb deletion. The second, in a previously undescribed family, arose by unequal homologous recombination between the same L1 and a colinear L1 element in intron 2 of COL4A6, resulting in a>40-kb deletion. L1 elements have contributed to the emergence of this locus as a site of frequent recombinations by diverse mechanisms. These give rise to AS-DL by disruption of type IV collagen and perhaps other as yet unidentified genes, evidenced by deletions as small as 13.4 kb.
位于Xq22染色体上的配对IV型胶原蛋白基因COL4A5和COL4A6的5'末端缺失会导致奥尔波特综合征（AS）及相关的弥漫性平滑肌瘤病（DL），后者是一种涉及食管、大气道和女性生殖道的弥漫性平滑肌肿瘤综合征。在本研究中，我们报告了两个缺失连接点的分离和特征。第一个缺失连接点出现在其他地方描述的一名患者中，是由一个非同源重组事件引起的，该事件将COL4A5第1内含子中的一个LINE-1（L1）重复元件与COL4A6第2内含子融合，导致13.4 kb的缺失。第二个缺失连接点出现在一个之前未描述过的家族中，是由COL4A6第2内含子中相同的L1与一个共线L1元件之间的不等位同源重组引起的，导致超过40 kb的缺失。L1元件通过多种机制促使该基因座成为频繁重组的位点。这些机制通过破坏IV型胶原蛋白以及可能其他尚未确定的基因导致AS-DL，小至13.4 kb的缺失就证明了这一点。
