J Pediatr Neurol 2017; 15(06): 316-324
DOI: 10.1055/s-0037-1603349
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Phenotypic Variability and mTOR Pathway Gene Aberrations in Familial Tuberous Sclerosis

Winnie S. Liang1, Shobana Sekar1, Sara Nasser1, Jonathan Adkins1, Lori Cuyugan1, Daniel Enriquez1, Sampath Rangasamy1, Vinodh Narayanan1
  • 1Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Arizona, United States
Further Information

Publication History

03 January 2017

16 April 2017

Publication Date:
22 May 2017 (eFirst)


Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that demonstrates variable severity, such that affected family members may have mild or severe disease. We performed exome and RNA sequencing of blood leukocytes from mild and severe cases across four families to identify mTOR pathway aberrations that may underlie phenotypic variability. In each family, we identified TSC1/TSC2 aberrations along with different mTOR pathway gene alterations, including base substitutions, deletions, and skewed allelic frequencies. Here, we describe the first reported DNA and RNA analysis of TSC families demonstrating mTOR pathway aberrations in mild and severe forms of the disease.

Supplementary Material