Clonal overgrowth of esophageal smooth muscle cells in diffuse leiomyomatosis-Alport syndrome caused by partial deletion in COL4A5 and COL4A6 genes
Clonal overgrowth of esophageal smooth muscle cells in diffuse leiomyomatosis-Alport syndrome caused by partial deletion in COL4A5 and COL4A6 genes
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DOI：
10.1016/j.matbio.2010.09.003
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发表时间：
2011-01-01
期刊：
影响因子：
6.9
通讯作者：
Ninomiya, Yoshifumi
中科院分区：
文献类型：
--
作者：
Oohashi, Toshitaka;Naito, Ichiro;Ninomiya, Yoshifumi
这是一项研究，研究对象是一名表现出弥漫性子宫肌瘤病-阿尔波特综合征(DL-ATS)所有特征的患者和她两岁的儿子，后者已经被诊断出患有阿尔波特综合征。14年前，患者接受了部分食道切除，然后空肠置换。最近，由于食道功能障碍，她接受了食道手术切除。利用她儿子的基因组DNA，高效地进行了X染色体上COL4A5和COL4A6的遗传分析。我们已经确定了一个新的长度为194-kb的缺失，包括Col4A5-COL4A6启动子以及几乎整个Col4A5的大内含子1和COL4A6的内含子2。为了揭示肿瘤的食道特异性发生与这些基因表达的关系，对未受影响的个体进行了IV型胶原α链的免疫组织化学分析。观察胃肠道内α5(IV)和α6(IV)链在食道中的特异性表达。此外，肌瘤中雄激素受体基因的CAG重复分析和免疫组织化学分析显示，接受X灭活的细胞在未受影响的等位基因上克隆性过度生长。这些结果可能表明，显性效应是由部分缺失的食道平滑肌特异性基因COL4A5和COL4A6引起的。(C)2010爱思唯尔B.V.保留所有权利。
This is a study of a patient who manifests all of the features of a diffuse leiomyomatosis-Alport syndrome (DL-ATS), and her two-year-old son who has already been diagnosed with Alport syndrome. Fourteen years ago, the patient underwent a partial esophageal resection followed by a replacement with jejunum. Recently, she underwent a surgical resection of the esophagus due to esophageal dysfunction. Genetic analyses of COL4A5 and COL4A6 on the X-chromosome were efficiently performed using the genomic DNA of her son. We have identified a novel deletion of 194-kb in length, encompassing COL4A5-COL4A6 promoters as well as nearly the entire large intron 1 of COL4A5 and intron 2 of COL4A6. To uncover the relationship of the esophagus-specific occurrence of the tumor and the expression of those genes, immunohistochemical analyses of type IV collagen alpha chains were conducted in the non-affected individuals. The esophageal smooth muscle-specific expression of alpha 5(IV) and alpha 6(IV) chains in the gastrointestinal tract was observed. Moreover, CAG repeat analysis of the androgen receptor gene and an immunohistochemical analysis in the leiomyoma revealed clonal overgrowth of the cells which received X-inactivation on the non-affected allele. These results may suggest that the dominant effect was caused by the partial deletion of the esophageal smooth muscle-specific genes, COL4A5 and COL4A6. (c) 2010 Elsevier B.V. All rights reserved.