EFFECTIVE USE OF NEXT GENERATION SEQUENCING FOR GENETIC DIAGNOSIS OF A PATIENT WITH A MOSAIC TSC2 VARIANT

Abstract

Aims: Tuberous sclerosis complex is a genetic disorder characterized by mutations in Tuberous Sclerosis Complex 1 (* 605284) or Tuberous Sclerosis Complex 2 (* 191092) genes. PALB2 (* 610355) gene has long been known to be associated with increased breast and pancreatic cancer risk. Its association with risk of stomach and lung cancers has also been established recently. In this case report, it is aimed to present a case of a 24-year-old female patient, who has been diagnosed with both novel mosaic Tuberous Sclerosis Complex 2 pathogenic variation and pathogenic PALB2 variation at the same time.

Case Report: A 24-year-old female patient was admitted to Trakya University Genetic Diseases Center with suspected tuberous sclerosis complex. Her primary complaints were a continuous headache and fatigue. She had no history of convulsion and seizure. There were bilateral facial angiofibromas around her nose. When genomic DNA was isolated, both novel mosaic Tuberous Sclerosis Complex 2 pathogenic variation and pathogenic PALB2 variation were observed.

Conclusion: This case report shows that in cancer predisposing syndromes, Next-generation sequencing is a powerful technique to portrait a detailed genetic profile of patient, investigating for any mosaicism or other risk alleles. 

Keywords

• Tuberous sclerosis,mosaicism,mutation

Kaynakça

1. 1. Nellist M, Brouwer RW, Kockx CE et al. Targeted Next generation sequencing reveals previously unidentified TSC1 and TSC2 mutations. BMC Med Genet 2015;16:10.
2. 2. Avgeris S, Fostira F, Vagena A et al. Mutational analysis of TSC1 and TSC2 genes in tuberous sclerosis complex patients from Greece. Sci Rep 2017;7(1):16697.
3. 3. Lee JEA, Li N, Rowley SM et al. Molecular analysis of PALB2-associated breast cancers. J Pathol 2018;245(1):53-60.
4. 4. Bleuyard JY, Butler RM, Esashi F. Perturbation of PALB2 function by the T413S mutation found in small cell lung cancer. Wellcome Open Res 2017;2:110.
5. 5. Serratì S, De Summa S, Pilato B et al. Next-generation sequencing: advances and applications in cancer diagnosis. Onco Targets and Ther 2016;9:7355–65.
6. 6. Richards S, Aziz N, Bale S et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17(5):405-24.
7. 7. Blackburn HL, Schroeder B, Turner C et al. Management of incidental findings in the era of Next-generation sequencing. Curr Genomics 2015;16(3):159-74.