PMID- 31018109
OWN - NLM
STAT- MEDLINE
DCOM- 20200508
LR  - 20211204
IS  - 1545-293X (Electronic)
IS  - 1527-8204 (Linking)
VI  - 20
DP  - 2019 Aug 31
TI  - Genetic Etiologies, Diagnosis, and Treatment of Tuberous Sclerosis Complex.
PG  - 217-240
LID - 10.1146/annurev-genom-083118-015354 [doi]
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that affects 
      multiple organ systems due to an inactivating variant in either TSC1 or TSC2, 
      resulting in the hyperactivation of the mechanistic target of rapamycin (mTOR) 
      pathway. Dysregulated mTOR signaling results in increased cell growth and 
      proliferation. Clinically, TSC patients exhibit great phenotypic variability, but 
      the neurologic and neuropsychiatric manifestations of the disease have the 
      greatest morbidity and mortality. TSC-associated epilepsy occurs in nearly all 
      patients and is often difficult to treat because it is refractory to multiple 
      antiseizure medications. The advent of mTOR inhibitors offers great promise in 
      the treatment of TSC-associated epilepsy and other neurodevelopmental 
      manifestations of the disease; however, the optimal timing of therapeutic 
      intervention is not yet fully understood.
FAU - Salussolia, Catherine L
AU  - Salussolia CL
AD  - F.M. Kirby Neurobiology Center, Translational Neuroscience Center, Department of 
      Neurology, Boston Children's Hospital, Harvard Medical School, Boston, 
      Massachusetts 02115, USA; email: mustafa.sahin@childrens.harvard.edu.
FAU - Klonowska, Katarzyna
AU  - Klonowska K
AD  - Division of Pulmonary and Critical Care Medicine and Division of Genetics, 
      Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 
      02115, USA.
FAU - Kwiatkowski, David J
AU  - Kwiatkowski DJ
AD  - Division of Pulmonary and Critical Care Medicine and Division of Genetics, 
      Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 
      02115, USA.
FAU - Sahin, Mustafa
AU  - Sahin M
AD  - F.M. Kirby Neurobiology Center, Translational Neuroscience Center, Department of 
      Neurology, Boston Children's Hospital, Harvard Medical School, Boston, 
      Massachusetts 02115, USA; email: mustafa.sahin@childrens.harvard.edu.
LA  - eng
GR  - P01 CA120964/CA/NCI NIH HHS/United States
GR  - U01 NS082320/NS/NINDS NIH HHS/United States
GR  - U54 HD090255/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
DEP - 20190424
PL  - United States
TA  - Annu Rev Genomics Hum Genet
JT  - Annual review of genomics and human genetics
JID - 100911346
RN  - 0 (Neuroprotective Agents)
RN  - 0 (TSC1 protein, human)
RN  - 0 (TSC2 protein, human)
RN  - 0 (Tuberous Sclerosis Complex 1 Protein)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - GR120KRT6K (Vigabatrin)
SB  - IM
MH  - Everolimus/therapeutic use
MH  - Gene Expression Regulation
MH  - Genotype
MH  - Humans
MH  - Mental Disorders/diagnosis/drug therapy/*genetics/metabolism
MH  - Mutation
MH  - Neurogenesis/drug effects/genetics
MH  - Neurons/drug effects/metabolism/pathology
MH  - Neuroprotective Agents/therapeutic use
MH  - Phenotype
MH  - Severity of Illness Index
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*genetics/metabolism
MH  - Tuberous Sclerosis/diagnosis/drug therapy/*genetics/metabolism
MH  - Tuberous Sclerosis Complex 1 Protein/*genetics/metabolism
MH  - Tuberous Sclerosis Complex 2 Protein/*genetics/metabolism
MH  - Vigabatrin/therapeutic use
OTO - NOTNLM
OT  - epilepsy
OT  - genetics
OT  - mTOR
OT  - rapamycin
OT  - tuberous sclerosis
EDAT- 2019/04/25 06:00
MHDA- 2020/05/10 06:00
CRDT- 2019/04/25 06:00
PHST- 2019/04/25 06:00 [pubmed]
PHST- 2020/05/10 06:00 [medline]
PHST- 2019/04/25 06:00 [entrez]
AID - 10.1146/annurev-genom-083118-015354 [doi]
PST - ppublish
SO  - Annu Rev Genomics Hum Genet. 2019 Aug 31;20:217-240. doi: 
      10.1146/annurev-genom-083118-015354. Epub 2019 Apr 24.