Yang Mei-Hua, Wang Zhong-Ke, Huang Yi, Lv Sheng-Qing, Zhang Chun-Qing, Zhu Yuan-Yuan, Yang Qing-Wu, Liu Shi-Yong
Epilepsy Center of PLA, Department of Neurosurgery, Xinqiao Hospital, Army Medical University, Chongqing, 400037, People's Republic of China.
Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, People's Republic of China.
Childs Nerv Syst. 2021 Jan;37(1):253-257. doi: 10.1007/s00381-020-04702-7. Epub 2020 Jun 12.
Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by hamartomas in multiple organ systems. The TSC1 and TSC2 genes have been identified as the genetic basis of TSC. Two gene tests were used for definitive genetic diagnosis.
In our study, the case of a Chinese pediatric patient with seizures, hypomelanotic macules, hyperpigmented patches, multiple parenchymal lesions in the ventricle, and developmental retardation is detailed. Whole-genome sequencing (WGS) and multiplex ligation-dependent probe amplification (MLPA) were employed to detect genetic variations and copy number variations of TSC1 and TSC2.
A novel heterozygous nonsense mutation in the TSC2 gene (c.3751A>T, p.Lys1251Ter) was identified in a Chinese pediatric patient suffering from TSC, whose unaffected parents did not carry this mutation. The mutation was classified as "pathogenic" according to the American College of Medical Genetics (ACMG) guidelines.
WGS was carried out to definitively diagnose and detect variations in the exon and noncoding region of the gene and copy number variations in the whole genome simultaneously. For diseases with complex genetic mechanisms, WGS as the first-line test can be efficient and cost-effective for clinical diagnosis.
结节性硬化症（TSC）是一种常染色体显性多系统疾病，其特征为多个器官系统出现错构瘤。TSC1和TSC2基因已被确定为TSC的遗传基础。采用两种基因检测方法进行明确的基因诊断。
在我们的研究中，详细介绍了一名患有癫痫、色素减退斑、色素沉着斑、脑室内多个实质病变及发育迟缓的中国儿科患者的病例。采用全基因组测序（WGS）和多重连接依赖探针扩增（MLPA）检测TSC1和TSC2的基因变异和拷贝数变异。
在一名患有TSC的中国儿科患者中，在TSC2基因中鉴定出一种新的杂合无义突变（c.3751A>T，p.Lys1251Ter），其未受影响的父母未携带此突变。根据美国医学遗传学学会（ACMG）指南，该突变被分类为“致病性”。
进行全基因组测序以同时明确诊断并检测基因外显子和非编码区的变异以及全基因组的拷贝数变异。对于遗传机制复杂的疾病，全基因组测序作为一线检测方法可在临床诊断中高效且经济有效。
