Assessment of Tuberous Sclerosis Complex Associated With Renal Lesions by Targeted Next-generation Sequencing in Mainland China
Assessment of Tuberous Sclerosis Complex Associated With Renal Lesions by Targeted Next-generation Sequencing in Mainland China
复制标题
中国大陆的结节性硬化症与肾脏病变相关的靶向二代测序评估
DOI：
10.1016/j.urology.2016.10.056
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发表时间：
2017-03-01
期刊：
影响因子：
2.1
通讯作者：
Zhang, Yushi
中科院分区：
文献类型：
--
作者：
Cai, Yi;Li, Hanzhong;Zhang, Yushi
目的鉴定结节性硬化症（TSC）患者与肾脏病变相关的TSC1和TSC2突变，并探讨其基因型与表型之间的关系。材料和方法我们使用下一代测序（NGS）分析了43例伴有肾脏病变的TSC患者。我们还进行了Sanger测序来验证NGS结果。结果：我们使用NGS对43例伴有肾脏病变的TSC患者进行了全面的突变分析。43例患者中有41例（95%）至少有1个可检测到的TSC1或TSC2基因突变。我们发现了14个新的核苷酸改变，包括11个新的小突变和3个大缺失突变。我们的研究通过分析TSC2基因突变与临床特征的相关关系，发现TSC2基因突变的患者比非TSC2基因突变的患者出现低黑素斑、牙釉质凹陷和更大的血管平滑肌脂肪瘤（AMLs）的频率更高。结论与非TSC2突变患者相比，TSC2突变患者出现低黑色素斑和牙釉质凹陷的频率更高，肾脏aml也更大。TSC1或TSC2基因大缺失和移码突变的患者比其他类型突变的患者表现出更大的AML直径。(C) 2016 Elsevier Inc.
OBJECTIVE To identify the TSC1 and TSC2 mutations in patients with tuberous sclerosis complex (TSC) associated with renal lesions, and to explore the relationship between genotypes and phenotypes.MATERIALS AND METHODS We analyzed 43 individuals affected with TSC accompanied by renal lesions using nextgeneration sequencing (NGS). We also performed Sanger sequencing to validate the NGS results.RESULTS We reported a comprehensive mutation analysis of 43 affected individuals with TSC accompanied by renal lesions using NGS. Forty-one of 43 patients (95%) had at least 1 detectable mutation in the TSC1 or TSC2 gene. We identified 14 novel nucleotide alterations, including 11 novel small mutations and 3 large-deletion mutations for the first time. Our study showed that patients with TSC2 mutations had higher frequency of hypomelanotic macules and dental enamel pits and larger angiomyolipomas (AMLs) than patient populations with non-TSC2 mutations through analysis of the correlated mutation findings with clinical features.CONCLUSION In conclusion, patients with TSC2 mutations had higher frequency of hypomelanotic macules and dental enamel pits, along with larger renal AMLs, compared with patient populations with non-TSC2 mutations. Patients with large deletions and frameshift mutations of the TSC1 or TSC2 gene showed larger AML diameters than patients with other kinds of mutations. (C) 2016 Elsevier Inc.