Table_4_Clinical Manifestations of Alport Syndrome-Diffuse Leiomyomatosis Patients With Contiguous Gene Deletions in COL4A6 and COL4A5.DOCX

Alport syndrome-diffuse leiomyomatosis is a rare type of X-linked Alport syndrome resulting from contiguous deletions of 5′ exons of COL4A5 and COL4A6. Studies have suggested that the occurrence of diffuse leiomyomatosis is associated with the characteristic localisation of the COL4A6 gene deletion break point. An electronic database was searched for all studies accessing AS-DL to analyze the clinical characteristics, gene deletion break points of patients with AS-DL, and the pathogenesis of AS-DL. It was found that the proportion of de novo mutations of AS-DL was significantly higher in female probands than male probands (78 vs. 44%). Female patients with AS-DL had a mild clinical presentation. The incidence of proteinuria and ocular abnormalities was much lower in female probands than in male probands, and there was generally no sensorineural hearing loss or chronic kidney disease (CKD), which progressed to Stage 3 in female probands. The contiguous deletion of the 5' exons of COL4A5 and COL4A6, with the break point within the intron 3 of COL4A6, was the critical genetic defect causing AS-DL. However, the pathogenesis of characteristic deletion of COL4A6 that contributes to diffuse leiomyomatosis is still unknown. In addition, characteristic contiguous deletion of COL4A5 and COL4A6 genes in AS-DL may be related to transposed elements (TEs).

阿尔波特综合征-弥漫性平滑肌瘤病是一种罕见的X连锁阿尔波特综合征，由COL4A5和COL4A6基因5'外显子的连续缺失所引起。研究指出，弥漫性平滑肌瘤病的出现与COL4A6基因缺失断点的特征性定位密切相关。通过电子数据库检索了所有涉及AS-DL的研究，以分析AS-DL患者的临床特征、基因缺失断点以及AS-DL的发病机制。研究发现，AS-DL的全新突变在女性患者中显著高于男性患者（分别为78%和44%）。AS-DL的女性患者临床表现较轻。女性患者的蛋白尿和眼部异常发生率远低于男性患者，且通常不存在感音神经性听力丧失或慢性肾脏病（CKD），在女性患者中未进展至3期。COL4A5和COL4A6基因5'外显子的连续缺失，其断点位于COL4A6基因的第3内含子内，是导致AS-DL的关键遗传缺陷。然而，导致弥漫性平滑肌瘤病的特征性COL4A6基因缺失的发病机制尚不清楚。此外，AS-DL中COL4A5和COL4A6基因的特征性连续缺失可能与转座元件（TEs）相关。