Detection of <i>TSC1</i>/<i>TSC2</i> mosaic variants in patients with cardiac rhabdomyoma and tuberous sclerosis complex by hybrid‐capture next‐generation sequencing

Wang, Siyu; Sun, Hairui; Wang, Jianbin; Gu, Xiaoyan; Han, Lu; Wu, Yougui; Yan, He; Lv, Han; Zhang, Hongjia; He, Yihua

doi:10.1002/mgg3.1802

Cited by 5 publications

(1 citation statement)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Detection of TSC1/TSC2 mosaic variants in patients with cardiac rhabdomyoma and tuberous sclerosis complex by hybrid-capture next-generation sequencing [139] Hybrid capture sequencing of coding sequences and 10 kb upstream and downstream, with mean sequencing depth of 7423× in target regions. Confirmation of detected variants by ddPCR.…”

Section: Brain Samples From Intractable Epilepsy Patientsmentioning

confidence: 99%

The Genetics of Tuberous Sclerosis Complex and Related mTORopathies: Current Understanding and Future Directions

Man,

Di Scipio,

Grewal

et al. 2024

Genes

View full text Add to dashboard Cite

The mechanistic target of rapamycin (mTOR) pathway serves as a master regulator of cell growth, proliferation, and survival. Upregulation of the mTOR pathway has been shown to cause malformations of cortical development, medically refractory epilepsies, and neurodevelopmental disorders, collectively described as mTORopathies. Tuberous sclerosis complex (TSC) serves as the prototypical mTORopathy. Characterized by the development of benign tumors in multiple organs, pathogenic variants in TSC1 or TSC2 disrupt the TSC protein complex, a negative regulator of the mTOR pathway. Variants in critical domains of the TSC complex, especially in the catalytic TSC2 subunit, correlate with increased disease severity. Variants in less crucial exons and non-coding regions, as well as those undetectable with conventional testing, may lead to milder phenotypes. Despite the assumption of complete penetrance, expressivity varies within families, and certain variants delay disease onset with milder neurological effects. Understanding these genotype–phenotype correlations is crucial for effective clinical management. Notably, 15% of patients have no mutation identified by conventional genetic testing, with the majority of cases postulated to be caused by somatic TSC1/TSC2 variants which present complex diagnostic challenges. Advancements in genetic testing, prenatal screening, and precision medicine hold promise for changing the diagnostic and treatment paradigm for TSC and related mTORopathies. Herein, we explore the genetic and molecular mechanisms of TSC and other mTORopathies, emphasizing contemporary genetic methods in understanding and diagnosing the condition.

show abstract

Section: Brain Samples From Intractable Epilepsy Patientsmentioning

confidence: 99%