Ding Yifeng, Wang Ji, Zhou Shuizhen, Zhou Yuanfeng, Zhang Linmei, Yu Lifei, Wang Yi
Department of Neurology, Children's Hospital of Fudan University, Shanghai, China.
Front Genet. 2020 Mar 10;11:204. doi: 10.3389/fgene.2020.00204. eCollection 2020.
Tuberous sclerosis complex (TSC) is a genetic condition characterized by the occurrence of hamartomatous wounds stemming from the dysfunction of the mammalian target of rapamycin (mTOR) pathway. We investigated the clinical phenotypes and genetic variants in 243 unrelated probands and their families in China. Exome sequencing, targeted sequencing or multiplex ligation-dependent probe amplification (MLPA) was performed in 174 children with TSC, among whom 31 (17.82%) patients/families were identified as having pathogenic or likely pathogenic variants in the gene, 120 (68.97%) as having pathogenic or likely pathogenic variants in the gene and 23 (13.21%) as having no pathogenic or likely pathogenic variants identified (NMI). In the 31 patients with pathogenic or likely pathogenic variants, 10 novel variants were detected among 26 different variants. In all 120 patients with variants, 39 novel variants were found among a total of 107 different variants. We compared the phenotypes of the individuals with pathogenic variants, pathogenic variants and NMI. Patients with variants were first diagnosed at a younger age ( = 0.003) and had more retinal hamartomas ( = 0.003) and facial angiofibromas ( = 0.027) (age ≥ 3 years) than individuals with variants. Compared with individuals with pathogenic variants, NMI individuals had fewer cortical tubers ( = 0.003). Compared with individuals with pathogenic variants, NMI patients had more retinal hamartomas ( = 0.035), and compared with individuals with pathogenic variants, they had less epilepsy ( = 0.003) and fewer subependymal nodules (SENs) ( = 0.004).
结节性硬化症（TSC）是一种遗传性疾病，其特征是由雷帕霉素哺乳动物靶点（mTOR）通路功能障碍引发错构瘤性损伤。我们对中国243名无亲缘关系的先证者及其家族的临床表型和基因变异进行了研究。对174例TSC患儿进行了外显子组测序、靶向测序或多重连接依赖探针扩增（MLPA），其中31例（17.82%）患者/家族被鉴定为该基因存在致病性或可能致病性变异，120例（68.97%）为该基因存在致病性或可能致病性变异，23例（13.21%）未鉴定出致病性或可能致病性变异（NMI）。在31例具有致病性或可能致病性变异的患者中，在26种不同变异中检测到10种新变异。在所有120例具有变异的患者中，在总共107种不同变异中发现了39种新变异。我们比较了具有致病性变异、致病性变异和NMI个体的表型。与具有致病性变异的个体相比，具有致病性变异的患者首次诊断年龄更小（P = 0.003），视网膜错构瘤更多（P = 0.003），面部血管纤维瘤更多（P = 0.027）（年龄≥3岁）。与具有致病性变异的个体相比，NMI个体的皮质结节更少（P = 0.003）。与具有致病性变异的个体相比，NMI患者的视网膜错构瘤更多（P = 0.035），与具有致病性变异的个体相比，癫痫更少（P = 0.003），室管膜下结节（SENs）更少（P = 0.004）。
