Files and links (2)
Published, Version of Record (VoR)CC BY-NC V4.0, Open
Journal article
Genetics of tuberous sclerosis complex: implications for clinical practice
Application of clinical genetics, v 10, pp 1-8
21 Dec 2016
PMID: 28053551
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Tuberous sclerosis complex (TSC) is a multisystem disorder that results from heterozygous mutations in either
TSC1
or
TSC2
. The primary organ systems that are affected include the brain, skin, lung, kidney, and heart, all with variable frequency, penetrance, and severity. Neurological features include epilepsy, autism, and intellectual disability. There are more than 1,500 known pathogenic variants for
TSC1
and
TSC2
, including deletion, nonsense, and missense mutations, and all pathogenic mutations are inactivating, leading to loss of function effects on the encoded proteins TSC1 and TSC2. These proteins form a complex to constitutively inhibit mechanistic target of rapamycin (mTOR) signaling cascade, and as a consequence, mTOR signaling is constitutively active within all TSC-associated lesions. The mTOR inhibitors rapamycin (sirolimus) and everolimus have been shown to reduce the size of renal and brain lesions and improve pulmonary function in TSC, and these compounds may also decrease seizure frequency. The clinical application of mTOR inhibitors in TSC has provided one of the first examples of precision medicine in a neurodevelopmental disorder.
Metrics
Details
- Title
- Genetics of tuberous sclerosis complex: implications for clinical practice
- Creators
- Carolina Caban - Department of Neurology; Shriners Hospitals Pediatric Research Center, Temple University School of Medicine.Nubaira Khan - Department of Neurology; Shriners Hospitals Pediatric Research Center, Temple University School of Medicine.Daphne M Hasbani - St. Christopher's Hospital for ChildrenPeter B Crino - Department of Neurology; Shriners Hospitals Pediatric Research Center, Temple University School of Medicine.
- Publication Details
- Application of clinical genetics, v 10, pp 1-8
- Publisher
- Dove Medical Press
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000395276700001
- Scopus ID
- 2-s2.0-85007531077
- Other Identifier
- 991019168570504721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Genetics & Heredity