Table_3_Clinical Manifestations of Alport Syndrome-Diffuse Leiomyomatosis Patients With Contiguous Gene Deletions in COL4A6 and COL4A5.XLSX

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，其由COL4A5和COL4A6基因5'外显子的连续缺失引起。研究表明，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，对涉及阿尔波特综合征-弥漫性平滑肌瘤病的所有研究进行了分析，以探讨该病的临床特征、患者基因缺失断点以及其发病机制。研究发现，新发突变在女性受试者中的比例显著高于男性受试者（分别为78%和44%）。患有阿尔波特综合征-弥漫性平滑肌瘤病的女性患者临床表现较轻。与男性受试者相比，女性受试者的蛋白尿和眼部异常的发生率明显较低，通常不存在感音神经性听力丧失或慢性肾病（CKD），且女性受试者中未见疾病进展至第3期。COL4A5和COL4A6基因5'外显子的连续缺失，其中断点位于COL4A6基因内含子3中，是导致阿尔波特综合征-弥漫性平滑肌瘤病的关键遗传缺陷。然而，导致弥漫性平滑肌瘤病的COL4A6基因特征性缺失的发病机制尚不清楚。此外，阿尔波特综合征-弥漫性平滑肌瘤病中COL4A5和COL4A6基因的特征性连续缺失可能与转座元件（TEs）有关。