Comprehensive genetic and phenotype analysis of 95 individuals with mosaic tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a neurogenetic disorder due to loss-of-function TSC1 or TSC2 variants, characterized by tumors affecting multiple organs, including skin, brain, heart, lung, and kidney. Mosaicism for TSC1 or TSC2 variants occurs in 10%-15% of individuals diagnosed with TSC. Here, we report comprehensive characterization of TSC mosaicism by using massively parallel sequencing (MPS) of 330 TSC samples from a variety of tissues and fluids from a cohort of 95 individuals with mosaic TSC.

Ultrasensitive profiling of UV-induced mutations identifies thousands of subclinical facial tumors in tuberous sclerosis complex.

BackgroundTuberous sclerosis complex (TSC) is a neurogenetic syndrome due to loss-of-function mutations in TSC2 or TSC1, characterized by tumors at multiple body sites, including facial angiofibroma (FAF). Here, an ultrasensitive assessment of the extent and range of UV-induced mutations in TSC facial skin was performed.MethodsA multiplex high-sensitivity PCR assay (MHPA) was developed, enabling mutation detection at extremely low (<0.

Sporadic facial angiofibroma and sporadic angiomyolipoma mimicking tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a genetic syndrome due to mutations in either or , leading to the development of hamartomatous tumours at multiple body sites, including facial skin (facial angiofibroma (FAF)), brain (cortical tubers) and kidney (angiomyolipoma (AML)). In this report, we describe an individual with minimal TSC clinical features, who had 'no mutation identified' (NMI) by prior genetic testing in a clinical laboratory. Our massively parallel sequencing (MPS) analysis of multiple samples from different body sites and tumours (including blood, saliva, normal skin, AML and FAF) revealed an extraordinary situation in which FAF and AML had completely independent inactivating biallelic variants in not present in other matched samples.

Low-level mosaicism in tuberous sclerosis complex: prevalence, clinical features, and risk of disease transmission.

Purpose: To examine the prevalence and spectrum of mosaic variant allele frequency (MVAF) in tuberous sclerosis complex (TSC) patients with low-level mosaicism and correlate genetic findings with clinical features and transmission risk.

Methods: Massively parallel sequencing was performed on 39 mosaic TSC patients with 170 different tissue samples.

Results: TSC mosaic patients (MVAF: 0-10%, median 1.