Web of Science: 9 citations, Scopus: 10 citations, Google Scholar: citations,
Insight into response to mTOR inhibition when PKD1 and TSC2 are mutated
Cabrera López, Cristina (Institut d'Investigació Biomèdica Sant Pau)
Bullich Vilanova, Gemma (Institut d'Investigació Biomèdica Sant Pau)
Martí, Teresa (Institut d'Investigació Biomèdica Sant Pau)
Català, Violeta (Institut d'Investigació Biomèdica Sant Pau)
Ballarín Castan, José Aurelio (Institut d'Investigació Biomèdica Sant Pau)
Bissler, John J. (Pediatric Nephrology Department, Le Bonheur Children's Hospital, Memphis, TN USA)
Harris, Peter C. (Department of Biochemistry and Molecular Biology, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN USA)
Ars Criach, Elisabet (Institut d'Investigació Biomèdica Sant Pau)
Torra Balcells, Roser (Institut d'Investigació Biomèdica Sant Pau)

Date: 2015
Abstract: 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. 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. 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.
Note: Número d'acord de subvenció ISCIII/RETIC/REDinREN/RD06/0016
Note: Número d'acord de subvenció ISCIII/RETIC/RD012/0021
Note: Número d'acord de subvenció ISCIII/FEDER/FIS/PI12/01523
Note: Número d'acord de subvenció ISCIII/FEDER/FIS/PI13/01731
Note: Altres ajuts: Novartis Pharmaceutical
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Tuberous sclerosis complex ; ADPKD ; Polycystic ; Mtor inhibitors
Published in: BMC Medical Genetics, Vol. 16 (june 2015) , ISSN 1471-2350

PMID: 26077033
DOI: 10.1186/s12881-015-0185-y


7 p, 1.3 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació Biomèdica Sant Pau
Articles > Research articles
Articles > Published articles

 Record created 2018-01-31, last modified 2019-02-07



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