Editorial Comment

Abstract

Renal manifestations occur in 80% of patients with tuberous sclerosis complex (TSC), with angiomyolipomas (AMLs) representing the most common lesions. Although there have been a number of genotype and phenotype studies on TSC related to manifestations in other organ systems, 1 Hoogeveen-Westerveld M. Ekong R. Povey S. et al. Functional assessment of TSC2 variants identified in individuals with tuberous sclerosis complex. Hum Mutat. 2013; 34: 167-175 Crossref PubMed Scopus (46) Google Scholar , 2 Dabora S.L. Jozwiak S. Franz D.N. et al. Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. Am J Hum Genet. 2001; 68: 64-80 Abstract Full Text Full Text PDF PubMed Scopus (756) Google Scholar less is known about the role specific mutations play in the development and severity of renal tumors. In this study, the authors investigate the correlation of TSC1 and TSC2 mutations with renal manifestations using next-generation sequencing. In addition to reporting 14 novel putative pathogenic mutations, the authors make several genotype and phenotype assertions: (1) mutations in TSC2 are more frequently associated with AMLs than non-TSC2 mutations; (2) mutations in TSC2 are associated with larger AMLs than non-TSC2 mutations; and (3) large deletions and frameshift mutations are associated with larger AMLs than other types of mutations. Although the sample size is small, the data are compelling.