• Linli Liu, Chunshui Yu, and Gaowu Yan.
• Department of Dermatology, Suining Central Hospital, Suining, People's Republic of China.
• Medicine (Baltimore). 2022 Jan 21; 101 (3): e28666e28666.

RationaleTuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by facial angiofibromas, epilepsy, intellectual disability, and the development of hamartomas in several organs, including the heart, kidneys, brain, and lungs. Mutations in either TSC1 or TSC2 result in dysregulated mTOR activation, leading to the occurrence of TSC.Patient ConcernsA 44-year-old man was hospitalized for acute lumbago and hematuria.DiagnosisThe patient presented with facial angiofibromas, epilepsy, fibrous plaques, periungual fibroma, renal angiomyolipomas (AML), pulmonary lymphangioleiomyomatosis (LAM), liver hamartomas, and osteosclerosis. A diagnosis of TSC was made based on clinical manifestations.InterventionsNext-generation sequencing (NGS) was performed to screen for potential variants, which were verified using Sanger sequencing. The final variant was analyzed using a minigene assay.OutcomesA potentially pathogenic novel TSC2 variant (NM_000548.4, c.336_336 + 15delGGTAAGGCCCAGGGCG) was identified using NGS and confirmed using Sanger sequencing. The in vitro minigene assay showed that the variant c.336_336 + 15delGGTAAGGCCCAGGGCG caused erroneous integration of a 74 bp sequence into intron 4. This novel variant was not found in his unaffected parents or 100 unrelated healthy controls.LessonsWe identified a novel heterozygous TSC2 variant, c.336_336 + 15delGGTAAGGCCCAGGGCG, in a patient with classical TSC and demonstrated that this variant leads to aberrant splicing using a minigene assay. Our results extend the understanding of the mutational spectrum of TSC2.Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.

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