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GENATLAS PHENOTYPE
last update : 01-06-2009
Symbol TSC1
Location 9q34.13
Name tuberous sclerosis 1
Corresponding gene TSC1
related resource TSC Variation database
Other symbol(s) TSC
Main clinical features
  • development of hamartomas in cerebral cortex, responsible of seizures, mental retardation and mental disorder including autism, cortical tuber, hamartomas in other organs, including subependymal nodules, facial angiofibromas, subungual fibromas, forehead plaques, shagreen patches, cardiac rhabdomyomas and renal angiomyololipomas
  • Genetic determination autosomal dominant
    Related entries including lymphangioleiomyomatosis (OMIM 606690)
    Function/system disorder neurology
    Type disease
    Gene product
    Name hamartin (TSC1)
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
    nonsense   abnormal protein/loss of function  
    frameshift   abnormal protein/loss of function  
    various types     with some cases of germline mosaicism, 47p100 of base substitution of which 85p100 were NS, 17p100 of small deletions 28 bp or less 36p100 small deletions or less than 23 bp, most of them removing an element of a tandem repeat 10-15p100 of sporadic cases
    unknown   abnormal protein/loss of function two-hit mechanism of biallelic inactivation of TSC1 or TSC2, leading to activation of FRAP1 and to subependymal giant cell astrocytomas
    Remark(s) . specific amino-acid substitutions close to the N-terminal of TSC1 reduce steady-state levels of TSC1, resulting in the activation of FRAP1signalling and leading to the symptoms of TSC (Nellist 2009)
  • mutations in either TSC1 or TSC2 alone can lead to polycystic kidney disease, but renal failure is uncommon (Hartman 2009)
  • loss of TSC1 in tumors causes endoplasmic reticulum (ER) stress and activates the unfolded protein response (UPR) (Ozcan 2008)