ISSN: 2149-2247 | E-ISSN: 2149-2549
Clinical and Molecular Spectrum of Tuberous Sclerosis Complex Patients: Identification of Three Novel Mutations [Erciyes Med J]
Erciyes Med J. 2021; 43(1): 54-60 | DOI: 10.14744/etd.2020.49765

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

Esra Işık1, Hüseyin Onay2, Tahir Atık1, Aslı Ece Solmaz2, Demet Terek3, Sarenur Gökben4, Hasan Tekgül2, Ertürk Levent5, Mehmet Kantar6, Nilgün Kültürsay3, Özgür Çoğulu1, Ferda Özkınay2
1Division of Pediatric Genetics, Department of Pediatrics, Ege University Faculty of Medicine, İzmir, Turkey
2Department of Medical Genetics, Ege University Faculty of Medicine, İzmir, Turkey
3Division of Neonatology, Department of Pediatrics, Ege University Faculty of Medicine, İzmir, Turke
4Division of Pediatric Neurology, Department of Pediatrics, Ege University Faculty of Medicine, İzmir, Turkey
5Division of Pediatric Cardiology, Department of Pediatrics, Ege University Faculty of Medicine, İzmir, Turkey
6Division of Pediatric Onkology, Department of Pediatrics, Ege University Faculty of Medicine, İzmir, Turkey

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

Esra Işık, Hüseyin Onay, Tahir Atık, Aslı Ece Solmaz, Demet Terek, Sarenur Gökben, Hasan Tekgül, Ertürk Levent, Mehmet Kantar, Nilgün Kültürsay, Özgür Çoğulu, Ferda Özkınay. Clinical and Molecular Spectrum of Tuberous Sclerosis Complex Patients: Identification of Three Novel Mutations. Erciyes Med J. 2021; 43(1): 54-60

Corresponding Author: Esra Işık, Türkiye
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