关键词: 结节性硬化症, TSC1, TSC2, 新致病变异

Abstract: Objective To identify the causative variants in 5 Chinese families with tuberous sclerosis complex (TSC) to provide genetic counseling and prenatal diagnosis. Methods Genetic counseling and clinical diagnosis were performed in 8 patients from five unrelated TSC families by teleconsultation. With informed consent obtained from the participants, 3 to 5 mL peripheral blood samples were collected from the probands and their family members for the extraction of genomic DNA. Candidate pathogenic variants were screened by panel sequencing (PS). The candidate pathogenic variants found in TSC1 and TSC2 by PS were validated by PCR-Sanger sequencing and bioinformatics analysis. Results All the pathogenic mutations were identified in the probands and their available family members. Causative variants in TSC1 or TSC2 were detected in all patients, including three reported variants and two novel variants. The two novel variants, TSC2:c.245G＞ A and TSC2: c.235delG, which were predicted to cause the nonsense variant p.(Trp82^*) and the frameshift variant p.(Val79Lysfs27^*) respectively was believed to introduce premature stop codons. The analysis of family co-segregation and bioinformatics were identified as very positive factors for pathogenicity. Conclusions This result provides more evidences for the genetic counseling and prenatal diagnosis in these families and expand the spectrum of TSC2 pathogenic variants.

Key words: tuberous sclerosis complex, TSC1, TSC2, novel pathogenic variant