Analysis of renal lesions in Chinese tuberous sclerosis complex patients with different types of TSC gene mutations

Abstract We sought to explore the relationship between renal lesion features and genetic mutations in tuberous sclerosis complex (TSC) patients. TSC patients with renal lesions were subjected to TSC1/2 gene next-generation sequencing (NGS). TSC1/2 mutation types and imaging examinations were screened for combined analysis of genetic and clinical features. Seventy-three probands among TSC patients with renal lesions were included. Twenty affected relatives were also included. In total, 93 patients were included. Eighty patients (86.0%) had bilateral renal angiomyolipomas (AMLs), and one had epithelioid AML. Two patients had polycystic kidney disease, one had renal cell carcinoma, and one had Wilms tumor. Among the 73 probands, four had TSC1 mutations, 53 had TSC2 mutations, and 16 had no mutations identified (NMI). There was no statistically significant difference between TSC1 mutation, TSC2 mutation and NMI group (P= 0.309), or between familial and sporadic groups (P= 0.775) when considering AML size. There was no statistically significant difference between pathogenic/likely pathogenic and benign/likely benign/NMI groups (P= 0.363) or among patients with different mutation types of TSC2 (P= 0.906). The relationship between the conditions of TSC gene mutations and the severity of renal lesions still needs more analysis. Patients with NMI, particularly those with familial disease, need more attention because the pathogenesis remains unknown.

摘要 本研究旨在探讨结节性硬化症（tuberous sclerosis complex, TSC）患者肾脏病变特征与基因突变之间的关联。本研究对合并肾脏病变的TSC患者开展TSC1/2基因下一代测序（next-generation sequencing, NGS），筛选TSC1/2突变类型及影像学检查结果，以联合分析遗传学与临床特征。本研究共纳入73例肾脏病变型TSC先证者，同时纳入20例受累亲属，总计93例患者。其中80例（86.0%）为双侧肾血管平滑肌脂肪瘤（renal angiomyolipomas, AMLs），1例合并上皮样肾血管平滑肌脂肪瘤（epithelioid AML）；2例罹患多囊肾，1例合并肾细胞癌，1例并发肾母细胞瘤。在73例先证者中，4例检出TSC1突变，53例检出TSC2突变，16例未检出突变（no mutations identified, NMI）。针对肾血管平滑肌脂肪瘤体积进行分析时，TSC1突变组、TSC2突变组与未检出突变组之间无统计学差异（P=0.309），家族性与散发性病例组之间亦无统计学差异（P=0.775）。致病性/可能致病性突变组与良性/可能良性/未检出突变组之间无统计学差异（P=0.363），不同TSC2突变类型患者组间亦无统计学差异（P=0.906）。TSC基因突变状态与肾脏病变严重程度之间的关联仍需进一步分析。未检出突变的患者，尤其是家族性病例，需得到更多关注，因其发病机制尚未明确。