Genetic Heterogeneity in Tuberous Sclerosis

Smith, Moyra; Yoshiyama, Kazuhiro; Wagner, Christel; Flodman, Pamela; Smith, Barbara A.

doi:10.1111/j.1749-6632.1991.tb37769.x

Cited by 4 publications

(2 citation statements)

References 19 publications

(3 reference statements)

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“…Up to 90% of patients suffer from epilepsy, and almost 50% have intellectual disabilities 1 . TSC is caused by a heterozygous mutation in either TSC1 2 3 or TSC2 4 5 which encode for hamartin (TSC1) and tuberin (TSC2), respectively 6 . These two proteins interact with each other 7 to form a functional heterodimeric complex that controls different aspects of cellular metabolism by its GTPase activating function towards the Ras homolog enriched in brain protein (RHEB) 8 .…”

mentioning

confidence: 99%

PAK2 is an effector of TSC1/2 signaling independent of mTOR and a potential therapeutic target for Tuberous Sclerosis Complex

Alves

Fuhler

Queiroz

et al. 2015

Sci Rep

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Tuberous sclerosis complex (TSC) is caused by inactivating mutations in either TSC1 or TSC2 and is characterized by uncontrolled mTORC1 activation. Drugs that reduce mTOR activity are only partially successful in the treatment of TSC, suggesting that mTOR-independent pathways play a role in disease development. Here, kinome profiles of wild-type and Tsc2−/− mouse embryonic fibroblasts (MEFs) were generated, revealing a prominent role for PAK2 in signal transduction downstream of TSC1/2. Further investigation showed that the effect of the TSC1/2 complex on PAK2 is mediated through RHEB, but is independent of mTOR and p21RAC. We also demonstrated that PAK2 over-activation is likely responsible for the migratory and cell cycle abnormalities observed in Tsc2−/− MEFs. Finally, we detected high levels of PAK2 activation in giant cells in the brains of TSC patients. These results show that PAK2 is a direct effector of TSC1-TSC2-RHEB signaling and a new target for rational drug therapy in TSC.

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mentioning

confidence: 99%

PAK2 is an effector of TSC1/2 signaling independent of mTOR and a potential therapeutic target for Tuberous Sclerosis Complex

Alves

Fuhler

Queiroz

et al. 2015

Sci Rep

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“…We calculated the Shannon-Weiner diversity index for mosquitoes collected in our pilot surveys. Shannon-Weiner diversity was used because it accounts for both species richness and abundance and is the most commonly used diversity index in ecology literature along with being relatively sensitive to site differences (Smith and Smith 2014).…”

Section: Methodsmentioning

confidence: 99%

A preliminary investigation of canine heartworm infection rates in Western North Carolina

Bennett,

Zinna

2023

BIOS

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Dirofilaria immitis, more commonly known as canine heartworm, is a parasitic nematode that leads to heartworm disease in dogs. Adult heartworms occupy the heart and lungs of dogs and prevent these organs from functioning properly. Anecdotal evidence suggested that several counties in Western North Carolina showed a trend of heartworm incidence rates that were lower than the incidence rates of both North Carolina and the United States. This study looked to investigate this anecdotal trend using data from the Companion Animal Parasite Council. Public data confirm that both Madison and Buncombe County have lower rates of heartworm infection than North Carolina as a whole. In order to help explain this trend we conducted a pilot survey using Buncombe County as a model of mosquito species diversity in Western North Carolina. We trapped mosquitoes at three sites in Buncombe County from July 2020 to October 2020. Our mosquito diversity estimate was used to predict expected rates of heartworm prevalence and found a substantial difference between the actual and expected heartworm prevalence in Buncombe County. It is possible that factors other than mosquito diversity contribute to low heartworm prevalence in Buncombe County and in other counties in Western North Carolina.

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Cytogenetic and molecular analysis of chromosome 11q23 abnormalities in leukaemia

Young

1992

Baillière's Clinical Haematology

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Genetic Heterogeneity in Tuberous Sclerosis

Cited by 4 publications

References 19 publications

PAK2 is an effector of TSC1/2 signaling independent of mTOR and a potential therapeutic target for Tuberous Sclerosis Complex

PAK2 is an effector of TSC1/2 signaling independent of mTOR and a potential therapeutic target for Tuberous Sclerosis Complex

A preliminary investigation of canine heartworm infection rates in Western North Carolina

Cytogenetic and molecular analysis of chromosome 11q23 abnormalities in leukaemia

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