Ni Kun, Yu Xiaolong, Ma Jiehui, Sun Dan
Department of Neurology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430014, China.
Department of Emergency and Critical Care Center, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430014, China.
Acta Epileptol. 2025 Aug 1;7(1):37. doi: 10.1186/s42494-025-00227-1.
Tuberous sclerosis complex (TSC), an inherited neurocutaneous disorder, is caused by variants in the TSC1 or TSC2 genes. The mosaic variants of TSC1 and TSC2 are scarcely detectable using the conventional next-generation sequencing (NGS). Therefore, this study aims to explore the detection and distribution of mosaic variants within affected families.
Through whole-exome sequencing (WES) or the TSC1/TSC2 panel to detect the variants of the TSC1 and TSC2 genes, the reaction system of droplet digital PCR (ddPCR) was designed to detect the mosaicism of these variants in affected families.
Genetic testing was carried out on 29 TSC patients via WES or the TSC1/TSC2 panel. The results showed that 27 patients had positive results in the TSC gene variant tests. Fourteen cases were confirmed as de novo variants, and the asymptomatic fathers or mothers of 4 patients were identified as somatic mosaics by ddPCR, with mosaic proportions of 0.8%, 24.18%, 8.02%, and 0.33% respectively.
The ddPCR holds the potential to improve diagnostic accuracy, genetic risk assessment, and clinical diagnosis rates. Consequently, it could potentially be adopted as one of the modalities for prompt clinical diagnosis.
结节性硬化症复合体（TSC）是一种遗传性神经皮肤疾病，由TSC1或TSC2基因的变异引起。使用传统的下一代测序（NGS）几乎无法检测到TSC1和TSC2的嵌合变异。因此，本研究旨在探索受影响家庭中嵌合变异的检测和分布情况。
通过全外显子组测序（WES）或TSC1/TSC2基因检测板来检测TSC1和TSC2基因的变异，设计液滴数字PCR（ddPCR）反应体系以检测这些变异在受影响家庭中的嵌合情况。
对29例TSC患者通过WES或TSC1/TSC2基因检测板进行基因检测。结果显示，27例患者的TSC基因变异检测呈阳性。14例被确认为新发变异，4例患者无症状的父亲或母亲通过ddPCR被鉴定为体细胞嵌合体，嵌合比例分别为0.8%、24.18%、8.02%和0.33%。
ddPCR有提高诊断准确性、遗传风险评估和临床诊断率的潜力。因此，它有可能被用作快速临床诊断的手段之一。
