Yi Cai1, Hanzhong Li1, Yushi Zhang2. 1. Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 2. 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.
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. MATERIALS AND 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. CONCLUSION: 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.
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. MATERIALS AND 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. CONCLUSION: 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.