Genotype and phenotype correlation in patients of tuberous sclerosis complex-associated renal angiomyolipomas

Abstract

Objective To study the correlation of genotype and phenotype in patients of tuberous sclerosis complex-associated renal angiomyolipomas (TSC-RAML). Methods The clinical and gene mutation data from 39 patients with TSC-RAML diagnosed in Peking Union Medical College Hospital were collected from January 2014 to December 2015. The clinical phenotype and genotype correlation associated with TSC-RAML was analyzed. A total of 39 patients (15 male, 24 female) were enrolled, with mean age of 28.4 years (range, 13~48). Results Five cases showed TSC1 gene mutation, thirty-two patients presented with TSC2 gene mutation and two cases didn't find any mutations. The mutations ratio of TSC1: TSC2 was 1: 6.4. Comparing to those with TSC1 gene mutation and no mutation identified, patients with TSC2 gene mutation had significantly higher frequency with hypomelanotic macules and dental enamel pits. The maximum diameter and clinical stage of patients with TSC2 gene mutation was significantly larger than patients with non-TSC2 gene mutations, along with higher frequency of AML bleeding risk and accepted invasive treatment. Conclusions The patients with TSC2 gene mutations presented higher frequency with hypomelanotic macules and dental enamel pits than those with non-TSC2 gene mutations. Comparing to those with TSC1 gene mutation and no mutation identified, the frequency of AML bleeding risk and loss of renal function was higher in patients with TSC2 gene mutations. Therefore, more active surveillance and treatment should be given to the patients of TSC-RAML with TSC2 gene mutations. Key words: Tuberous sclerosis complex; Genotype; Phenotype; Angiomyolipoma