73例儿童TSC1/2基因突变引起的结节性硬化症的临床特征和分子遗传学分析
{"_":"Clinical characteristics and molecular genetic analysis of 73 cases of tuberous sclerosis complex caused by gene mutations in children.","i":["TSC1/2"]}
摘要(中文译文)
本研究分析了73例结节性硬化症（TSC）患儿的临床及遗传学特征。通过探讨基因型-表型相关性，本研究旨在识别突变特征规律，以促进诊断、治疗及预后策略的优化。本回顾性研究分析了2018年2月至2025年6月期间就诊于南京医科大学附属儿童医院的TSC患儿。回顾了包括人口学资料和首发表现在内的临床数据，并采集外周血样本进行全外显子组测序。分类变量采用卡方检验进行统计分析。在73例TSC患儿中，62例（85%）诊断为癫痫，其中56例（90%）以惊厥发作为首发表现。观察到的发作类型包括癫痫性痉挛（25例）、全面性强直-阵挛发作（13例）、局灶性意识受损发作（10例）、局灶性意识保留发作（6例）、局灶继发双侧强直-阵挛发作（5例）、强直发作（1例）及失神发作（1例）。其他常见临床特征包括色素减退斑（44例）、皮质结节（34例）、智力障碍（24例）及室管膜下结节（22例）。基因检测在68例患者（93%）中检出TSC1或TSC2突变，对应71个不同的突变位点。其中14个变异（TSC1中2个，TSC2中12个）为新发现变异。突变谱包括无义突变、移码突变、错义突变及剪接位点突变类型，并鉴定出TSC1和TSC2的遗传性来源。TSC的临床表型具有高度异质性，基因型-表型关联复杂。14个新发现变异的鉴定扩展了TSC的已知突变谱，详细的基因型-表型分析为儿科人群的早期诊断、遗传咨询及个体化治疗策略提供了有价值的见解。因此，对于疑似TSC病例，早期基因检测对于确诊至关重要，并有助于实现个体化管理策略。
Abstract
This study analyzed the clinical and genetic characteristics of 73 pediatric patients with tuberous sclerosis complex (TSC). Through an examination of genotype-phenotype correlations, the research aimed to identify patterns in mutation characteristics to facilitate the optimization of diagnostic, therapeutic, and prognostic strategies. This retrospective study analyzed pediatric patients with TSC at Nanjing Medical University Children's Hospital between February 2018 and June 2025. Clinical data, including demographics and initial manifestations, were reviewed and peripheral blood samples were collected for whole-exome sequencing. Statistical analysis of categorical variables was performed using the chi-square test. Among the 73 pediatric TSC patients, 62 (85%) were diagnosed with epilepsy, with seizures being the initial manifestation in 56 (90%) of these cases. The observed seizure types included epileptic spasms ( = 25), generalized tonic-clonic seizure ( = 13), focal impaired consciousness seizure ( = 10), focal preserved consciousness seizure ( = 6), focal to bilateral tonic-clonic seizure ( = 5), tonic ( = 1), and absence ( = 1). Other common clinical features were hypopigmented macules ( = 44), cortical tubers ( = 34), intellectual disability ( = 24), and subependymal nodules ( = 22). Genetic testing identified or mutations in 68 patients (93%), corresponding to 71 distinct mutation sites. Fourteen variants (2 in , 12 in ) were novel. The spectrum of mutations included nonsense, frameshift, missense, and splice-site types, with both and inherited origins identified. The clinical phenotype of TSC is highly heterogeneous, with complex genotype-phenotype associations. The identification of 14 novel variants expands the known mutational spectrum of TSC, and the detailed genotype-phenotype analysis provides valuable insights for early diagnosis, genetic counseling, and personalized therapeutic strategies in pediatric populations. Early genetic testing is therefore crucial for diagnostic confirmation and enables personalized management strategies in cases of suspected TSC.
如何引用
AMA
Xiao Wu, Ming-Ying He, Hai-Feng Xu, Yan He, Xiao-Hui Min, Qi-Kai Zhao, et al. {"_":"Clinical characteristics and molecular genetic analysis of 73 cases of tuberous sclerosis complex caused by gene mutations in children.","i":["TSC1/2"]}. Frontiers in pediatrics. 2026; doi:10.3389/fped.2026.1795318.
APA
Xiao Wu, Ming-Ying He, Hai-Feng Xu, Yan He, Xiao-Hui Min, Qi-Kai Zhao, et al (2026). {"_":"Clinical characteristics and molecular genetic analysis of 73 cases of tuberous sclerosis complex caused by gene mutations in children.","i":["TSC1/2"]}. Frontiers in pediatrics. https://doi.org/10.3389/fped.2026.1795318
GB/T 7714
Xiao Wu, Ming-Ying He, Hai-Feng Xu, Yan He, Xiao-Hui Min, Qi-Kai Zhao, et al. {"_":"Clinical characteristics and molecular genetic analysis of 73 cases of tuberous sclerosis complex caused by gene mutations in children.","i":["TSC1/2"]}[J]. Frontiers in pediatrics, 2026 doi:10.3389/fped.2026.1795318.
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