ABSTRACT Mosaicism is relatively common in Tuberous Sclerosis Complex (TSC) but can be difficult to detect using routine diagnostic tests, particularly when the variant allele frequency (VAF) is low. We describe two cases of mosaic TSC diagnosed using an ultra‐deep sequencing approach in multiple tissues and review the literature about this topic in order to discuss new diagnostic paradigms. In the first case, further testing was prompted by the presence of angiomyolipomas in the otherwise unaffected 51‐year‐old father of a woman diagnosed with TSC2; the familial pathogenic variant was present with a very low VAF in angiomyolipoma tissue and peripheral blood. The second case, a 17‐year‐old boy diagnosed with infantile myofibromatosis, presented dermatological and brain MRI findings suggestive of TSC; a TSC1 pathogenic variant was first identified on DNA extracted from angiofibroma biopsy, and then confirmed on non‐lesional skin, peripheral blood, and saliva. The identification of the causative TSC1 / 2 variant is crucial to provide appropriate management and genetic counseling for family planning. Most mosaic individuals in the literature have cutaneous features of TSC; in the presence of an accessible lesion, we recommend considering a tissue biopsy to have a higher chance of identifying a low‐level mosaicism.
Ambrosetti et al. (Sun,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: