title: Clinical and Molecular Assessment in a Female with Fragile X Syndrome and Tuberous Sclerosis.
abstract: OBJECTIVE
  Fragile X syndrome (FXS) and tuberous sclerosis (TSC) are genetic disorders that result in intellectual disability and an increased prevalence of autism spectrum disorders (ASD). While the clinical presentation of each disorder is distinct, the molecular causes are linked to a disruption in the mTORC1 (mammalian Target of Rapamycin Complex 1) and ERK1/2 (Extracellular signal-Regulated Kinase) signaling pathways.
  
  
  METHODS
  We assessed the clinical and molecular characteristics of an individual seen at the UC Davis MIND Institute with a diagnosis of FXS and TSC. Clinical evaluation of physical, behavioral, and cognitive impairments were performed. Additionally, total and phosphorylated proteins along the mTORC1 and ERK1/2 pathways were measured in primary fibroblast cell lines from the proband.
  
  
  RESULTS
  In this case the phenotypic effects that result in a human with both FXS and TSC are shown to be severe. Changes in mTORC1 and ERK1/2 signaling proteins and global protein synthesis were not found to be noticeably different between four cohorts (typically developing,FMR1full mutation,FMR1full mutation andTSC1loss of function mutation, andTSC1loss of function mutation); however cohort sizes prevented stringent comparisons.
  
  
  CONCLUSIONS
  It has previously been suggested that disruption of the mTORC1 pathway was reciprocal in TSC and FXS double knock-out mouse models so that the regulation of these pathways were more similar to wild-type mice compared to mice harboring aFmr1-/yorTsc2-/+mutation alone. However, in this first reported case of a human with a diagnosis of both FXS and TSC, substantial clinical impairments, as a result of these two disorders were observed. Differences in the mTORC and ERK1/2 pathways were not clearly established when compared between individuals with either disorder, or both.
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, USA.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Yrigollen
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pacini
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Nobile
authors.affiliation: Department of Pediatrics, University of California, Davis, USA.
authors.forename: Reymundo
authors.initials: R
authors.lastname: Lozano
authors.affiliation: Department of Pediatrics, University of California, Davis, USA; MIND Institute, University of California, Davis, USA.
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Hagerman
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy; VIB Center for the Biology of Disease and Center for Human Genetics, Leuven, Belgium; Department of Fundamental Neuroscience, University of Lausanne, Lausanne, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bagni
authors.affiliation: MIND Institute, University of California, Davis, USA; Department of Biochemistry and Molecular Medicine, University of California, Davis, USA.
authors.forename: Flora
authors.initials: F
authors.lastname: Tassone
keywords: ERK1/2; Fragile X syndrome; Protein synthesis; Tuberous sclerosis; mTORC1