Insight into response to mTOR inhibition when PKD1 and TSC2 are mutated

Background: Mutations in TSC1 or TSC2 cause the tuberous sclerosis complex (TSC), while mutations in PKD1 or PKD2 cause autosomal dominant polycystic kidney disease (ADPKD). PKD1 lays immediately adjacent to TSC2 and deletions involving both genes, the PKD1/TSC2 contiguous gene syndrome (CGS), are c...

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Autores: Cabrera-Lopez, C, Bullich, G, Marti, T, Catala, V, Ballarin, J, Bissler, JJ, Harris, PC, Ars, E, Torra, R
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p8633
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=8633
http://ddd.uab.cat/record/185353
Access Level:acceso abierto
Palabra clave:Tuberous sclerosis complex
ADPKD
Polycystic
mTOR inhibitors
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spelling Insight into response to mTOR inhibition when PKD1 and TSC2 are mutatedCabrera-Lopez, CBullich, GMarti, TCatala, VBallarin, JBissler, JJHarris, PCArs, ETorra, RTuberous sclerosis complexADPKDPolycysticmTOR inhibitorsBackground: Mutations in TSC1 or TSC2 cause the tuberous sclerosis complex (TSC), while mutations in PKD1 or PKD2 cause autosomal dominant polycystic kidney disease (ADPKD). PKD1 lays immediately adjacent to TSC2 and deletions involving both genes, the PKD1/TSC2 contiguous gene syndrome (CGS), are characterized by severe ADPKD, plus TSC. mTOR inhibitors have proven effective in reducing angiomyolipoma (AML) in TSC and total kidney volume in ADPKD but without a positive effect on renal function. Methods and results: We describe a patient with independent truncating PKD1 and TSC2 mutations who has the expected phenotype for both diseases independently instead of the severe one described in PKD1/TSC2-CGS. Treatment with mTOR inhibitors reduced the AML and kidney volume for 2 years but thereafter they resumed growth; no positive effect on renal function was seen throughout. This is the first case addressing the response to mTOR treatment when independent truncating mutations in PKD1 and TSC2 are present. Conclusions: This case reveals that although PKD1 and TSC2 are adjacent genes and there is likely cross-talk between the PKD1 and TSC2 signalling pathways regulating mTOR, having independent TSC2 and PKD1 mutations can give rise to a milder kidney phenotype than is typical in PKD1/TSC2-CGS cases. A short-term beneficial effect of mTOR inhibition on AML and total kidney volume was not reflected in improved renal function.BIOMED CENTRAL LTD2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=8633http://ddd.uab.cat/record/185353BMC Medical GeneticsISSN: 14712350reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p86332026-06-14T12:41:47Z
dc.title.none.fl_str_mv Insight into response to mTOR inhibition when PKD1 and TSC2 are mutated
title Insight into response to mTOR inhibition when PKD1 and TSC2 are mutated
spellingShingle Insight into response to mTOR inhibition when PKD1 and TSC2 are mutated
Cabrera-Lopez, C
Tuberous sclerosis complex
ADPKD
Polycystic
mTOR inhibitors
title_short Insight into response to mTOR inhibition when PKD1 and TSC2 are mutated
title_full Insight into response to mTOR inhibition when PKD1 and TSC2 are mutated
title_fullStr Insight into response to mTOR inhibition when PKD1 and TSC2 are mutated
title_full_unstemmed Insight into response to mTOR inhibition when PKD1 and TSC2 are mutated
title_sort Insight into response to mTOR inhibition when PKD1 and TSC2 are mutated
dc.creator.none.fl_str_mv Cabrera-Lopez, C
Bullich, G
Marti, T
Catala, V
Ballarin, J
Bissler, JJ
Harris, PC
Ars, E
Torra, R
author Cabrera-Lopez, C
author_facet Cabrera-Lopez, C
Bullich, G
Marti, T
Catala, V
Ballarin, J
Bissler, JJ
Harris, PC
Ars, E
Torra, R
author_role author
author2 Bullich, G
Marti, T
Catala, V
Ballarin, J
Bissler, JJ
Harris, PC
Ars, E
Torra, R
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Tuberous sclerosis complex
ADPKD
Polycystic
mTOR inhibitors
topic Tuberous sclerosis complex
ADPKD
Polycystic
mTOR inhibitors
description Background: Mutations in TSC1 or TSC2 cause the tuberous sclerosis complex (TSC), while mutations in PKD1 or PKD2 cause autosomal dominant polycystic kidney disease (ADPKD). PKD1 lays immediately adjacent to TSC2 and deletions involving both genes, the PKD1/TSC2 contiguous gene syndrome (CGS), are characterized by severe ADPKD, plus TSC. mTOR inhibitors have proven effective in reducing angiomyolipoma (AML) in TSC and total kidney volume in ADPKD but without a positive effect on renal function. Methods and results: We describe a patient with independent truncating PKD1 and TSC2 mutations who has the expected phenotype for both diseases independently instead of the severe one described in PKD1/TSC2-CGS. Treatment with mTOR inhibitors reduced the AML and kidney volume for 2 years but thereafter they resumed growth; no positive effect on renal function was seen throughout. This is the first case addressing the response to mTOR treatment when independent truncating mutations in PKD1 and TSC2 are present. Conclusions: This case reveals that although PKD1 and TSC2 are adjacent genes and there is likely cross-talk between the PKD1 and TSC2 signalling pathways regulating mTOR, having independent TSC2 and PKD1 mutations can give rise to a milder kidney phenotype than is typical in PKD1/TSC2-CGS cases. A short-term beneficial effect of mTOR inhibition on AML and total kidney volume was not reflected in improved renal function.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=8633
http://ddd.uab.cat/record/185353
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=8633
http://ddd.uab.cat/record/185353
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BIOMED CENTRAL LTD
publisher.none.fl_str_mv BIOMED CENTRAL LTD
dc.source.none.fl_str_mv BMC Medical Genetics
ISSN: 14712350
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
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