Clinical and Molecular Spectrum of Tuberous Sclerosis Complex Patients: Identification of Three Novel Mutations

Abstract

Objective: Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome. TSC arises from mutations in either TSC1, at 9q34, or TSC2, at 16p13.3. Skin lesions, such as hypomelanotic macules, facial angiofibromas, shagreen patches, and ungual fibromas, are frequently seen in these patients. The present study aims to investigate clinical manifestations, molecular findings and phenotype-genotype correlations in 17 patients with TSC. Materials and Methods: TSC1 and TSC2 molecular analyses were performed on a next-generation sequencing platform (Illumina MiSeq). Variant interpretation was made in accordance with the American College of Medical Genetics 2015 recommendations. Results: Four patients carried a heterozygous mutation in TSC1, while the remaining seven carried mutations in TSC2. Three novel variants in TSC2 were defined. Sequencing failed to detect a mutation in six patients. In only one of these patients, multiplex ligation-dependent probe amplification (MLPA®) could be performed, and a large deletion in the TSC1 gene was detected. A wide spectrum of phenotypic features was noted throughout the study group. Dermatological findings were observed in almost all patients. Conclusion: In this study, in addition to the three novel mutations reported herein, the spectrum of TSC1 and TSC2 gene mutations and their phenotypes were reported.

Keywords

• tuberous sclerosis complex
• tsc1
• tsc2
• mtor inhibitor