Title
Missense mutations to the **TSC1** gene cause tuberous sclerosis complex Missense mutations to the **TSC1** gene cause tuberous sclerosis complex
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Leiden ,
Subject
Chemistry
Biology
Human medicine
Source (journal)
European journal of human genetics / European Society of Human Genetics. - Leiden
Volume/pages
17(2009) :3 , p. 319-328
ISSN
1018-4813
ISI
000263457800008
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterised by the development of hamartomas in a variety of organs and tissues. The disease is caused by mutations in either the TSC1 gene on chromosome 9q34 or the TSC2 gene on chromosome 16p13.3. The TSC1 and TSC2 gene products, TSC1 and TSC2, interact to form a protein complex that inhibits signal transduction to the downstream effectors of the mammalian target of rapamycin (mTOR). Here we investigate the effects of putative TSC1 missense mutations identified in individuals with signs and/or symptoms of TSC on TSC1-TSC2 complex formation and mTOR signalling. We show that specific amino-acid substitutions close to the N-terminal of TSC1 reduce steady-state levels of TSC1, resulting in the activation of mTOR signalling and leading to the symptoms of TSC.
E-info
https://repository.uantwerpen.be/docman/iruaauth/eef53c/ec51213.pdf
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