Application of targeted second-generation sequencing in the genetic diagnosis of tuberous sclerosis complex associated with renal complications

Abstract

Objective To evaluate the value of targeted second-generation sequencing (NGS) in the genetic diagnosis of tuberous sclerosis complex (TSC) associated with renal complications. Methods The clinical data of 43 patients (with 33 patients of definite diagnosis and 10 patients of possible diagnosis) with tuberous sclerosis complex associated with renal complications were analyzed. There were 26 females and 17 males with a mean age of 28 (10~48) years ranging from 10 to 48 years old. All patients had renal complications, including 39 renal angiomyolipomas, 3 renal cysts and 1 renal cell carcinoma. Written informed consents were signed, and 5ml peripheral blood was drawn for DNA extraction. Mutations of TSC1 and TSC2 genes were detected by the NGS technology, and then confirmed by Sanger sequencing. Results TSC1 or TSC2 pathogenetic mutants were identified in 39 patients (90.7%), which were consistent with clinical phenotypes and two non-significant mutations were identified in two individuals, while no mutation was detected in the other two cases. Fourteen novel mutations were reported for the first time, including 8 frameshift mutation, 3 deletion mutation, 2 nonsense mutation and 1 splicing mutation. Conclusion NGS is an accurate and less time-consuming technology in detecting TSC1 or TSC2 gene mutation, which has great value in genetic diagnosis of tuberous sclerosis complex associated with renal complications. Key words: Tuberous sclerosis complex(TSC); Next-generation sequencing; Genetic diagnosis; Kidney