title: Assessment of Tuberous Sclerosis Complex Associated With Renal Lesions by Targeted Next-generation Sequencing in Mainland China.
abstract: OBJECTIVE
  To identify the TSC1 and TSC2 mutations in patients with tuberous sclerosis complex (TSC) associated with renal lesions, and to explore the relationship between genotypes and phenotypes.
  
  
  METHODS
  We analyzed 43 individuals affected with TSC accompanied by renal lesions using next-generation sequencing (NGS). We also performed Sanger sequencing to validate the NGS results.
  
  
  RESULTS
  We reported a comprehensive mutation analysis of 43 affected individuals with TSC accompanied by renal lesions using NGS. Forty-one of 43 patients (95%) had at least 1 detectable mutation in the TSC1 or TSC2 gene. We identified 14 novel nucleotide alterations, including 11 novel small mutations and 3 large-deletion mutations for the first time. Our study showed that patients with TSC2 mutations had higher frequency of hypomelanotic macules and dental enamel pits and larger angiomyolipomas (AMLs) than patient populations with non-TSC2 mutations through analysis of the correlated mutation findings with clinical features.
  
  
  CONCLUSIONS
  In conclusion, patients with TSC2 mutations had higher frequency of hypomelanotic macules and dental enamel pits, along with larger renal AMLs, compared with patient populations with non-TSC2 mutations. Patients with large deletions and frameshift mutations of the TSC1 or TSC2 gene showed larger AML diameters than patients with other kinds of mutations.
authors.affiliation: Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Hanzhong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: zhangyushi2014@126.com.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D016147:Genes, Tumor Suppressor; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015994:Incidence; D007680:Kidney Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D014402:Tuberous Sclerosis / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins