Sporadic facial angiofibroma and sporadic angiomyolipoma mimicking tuberous sclerosis complex

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 TSC2, not present in other matched samples. This suggests that the two different lesions (AML and FAF) are not due to the same underlying germline or mosaic mutation, rather both are likely sporadic events. This case demonstrates the relevance of thorough clinical examination, high-coverage MPS of multiple tumours and matched normal tissues, and appropriate genetic counselling for individuals with marginal TSC features and possible TSC1 or TSC2 mosaicism.

Source: Journal of Medical Genetics - August 19, 2022 Category: Genetics & Stem Cells Authors: Klonowska, K., Thiele, E. A., Grevelink, J. M., Thorner, A. R., Kwiatkowski, D. J. Tags: Somatic mosaicism Source Type: research