TSC1
结节性硬化
TSC2
医学
外显率
错义突变
临床意义
肾细胞癌
基因检测
血管平滑肌脂肪瘤
室管膜下巨细胞星形细胞瘤
疾病
生物信息学
突变
表型
肿瘤科
病理
基因
PI3K/AKT/mTOR通路
内科学
遗传学
癌症研究
星形细胞瘤
生物
胶质瘤
肾
细胞凋亡
作者
Georgios Papageorgiou,Nikolaos Skouteris,Christos Valavanis,Gabriela-Monica Stanc,Efthymia Souka,Nikolaos Charalampakis
出处
期刊:Reviews on Recent Clinical Trials
[Bentham Science]
日期:2023-11-01
卷期号:18 (4): 304-312
标识
DOI:10.2174/0115748871258042230921052344
摘要
Background: Tuberous sclerosis complex (TSC) is a rare genetic disease that affects multiple organs and affects the quality of life. Mutations in TSC1 and TSC2 genes are causing dysregulations in the mammalian target of the rapamycin (mTOR) pathway, inducing mostly benign but also malignant tumors, including renal cell carcinoma (RCC). The diagnosis of TSC, based on established clinical and genetic criteria, is essential for the optimal surveillance and management of patients. Case Presentation: With the current report, we present the case of two sisters who were consequently diagnosed with early-stage chromophobe-like RCC, possibly familial given their young age. The younger sister also had a previous diagnosis of differentiated thyroid carcinoma, for which she had been treated properly. Genetic testing of both revealed the same heterozygous TSC2 variant that is currently regarded as a variant of unknown significance, while both patients did not fulfill the clinical criteria for the diagnosis of TSC. Owing to these data, we opted to manage and surveil both sisters as TSC patients, while we also considered the specific TSC2 variant to be pathogenic - but of low penetrance - based on clinical judgment and functional analyses. Furthermore, we discussed the implementation of mTOR inhibitors for the treatment of TSC complications. Conclusion: As novel pathogenic variants of TSC genes are constantly being explored, the identification of TSC variants of unknown significance in combination with absent clinical diagnostic criteria cannot exclude a TSC diagnosis. We support the implementation of clinical judgment in assisting the diagnosis of TSC, as well as the enrollment of patients in clinical trials due to the rarity of the disease.
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