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Rothmund-Thomson Syndrome: Insights from New Patients on the Genetic Variability Underpinning Clinical Presentation and Cancer Outcome

Biallelic mutations in RECQL4 gene, a caretaker of the genome, cause Rothmund-Thomson type-II syndrome (RTS-II) and confer increased cancer risk if they damage the helicase domain. We describe five families exemplifying clinical and allelic heterogeneity of RTS-II, and report the effect of pathogeni...

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Autores principales: Colombo, Elisa A., Locatelli, Andrea, Cubells Sánchez, Laura, Romeo, Sara, Elcioglu, Nursel H., Maystadt, Isabelle, Esteve Martínez, Altea, Sironi, Alessandra, Fontana, Laura, Finelli, Palma, Gervasini, Cristina, Pecile, Vanna, Larizza, Lidia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979380/
https://www.ncbi.nlm.nih.gov/pubmed/29642415
http://dx.doi.org/10.3390/ijms19041103
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author Colombo, Elisa A.
Locatelli, Andrea
Cubells Sánchez, Laura
Romeo, Sara
Elcioglu, Nursel H.
Maystadt, Isabelle
Esteve Martínez, Altea
Sironi, Alessandra
Fontana, Laura
Finelli, Palma
Gervasini, Cristina
Pecile, Vanna
Larizza, Lidia
author_facet Colombo, Elisa A.
Locatelli, Andrea
Cubells Sánchez, Laura
Romeo, Sara
Elcioglu, Nursel H.
Maystadt, Isabelle
Esteve Martínez, Altea
Sironi, Alessandra
Fontana, Laura
Finelli, Palma
Gervasini, Cristina
Pecile, Vanna
Larizza, Lidia
author_sort Colombo, Elisa A.
collection PubMed
description Biallelic mutations in RECQL4 gene, a caretaker of the genome, cause Rothmund-Thomson type-II syndrome (RTS-II) and confer increased cancer risk if they damage the helicase domain. We describe five families exemplifying clinical and allelic heterogeneity of RTS-II, and report the effect of pathogenic RECQL4 variants by in silico predictions and transcripts analyses. Complete phenotype of patients #39 and #42 whose affected siblings developed osteosarcoma correlates with their c.[1048_1049del], c.[1878+32_1878+55del] and c.[1568G>C;1573delT], c.[3021_3022del] variants which damage the helicase domain. Literature survey highlights enrichment of these variants affecting the helicase domain in patients with cancer outcome raising the issue of strict oncological surveillance. Conversely, patients #29 and #19 have a mild phenotype and carry, respectively, the unreported homozygous c.3265G>T and c.3054A>G variants, both sparing the helicase domain. Finally, despite matching several criteria for RTS clinical diagnosis, patient #38 is heterozygous for c.2412_2414del; no pathogenic CNVs out of those evidenced by high-resolution CGH-array, emerged as contributors to her phenotype.
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spelling pubmed-59793802018-06-10 Rothmund-Thomson Syndrome: Insights from New Patients on the Genetic Variability Underpinning Clinical Presentation and Cancer Outcome Colombo, Elisa A. Locatelli, Andrea Cubells Sánchez, Laura Romeo, Sara Elcioglu, Nursel H. Maystadt, Isabelle Esteve Martínez, Altea Sironi, Alessandra Fontana, Laura Finelli, Palma Gervasini, Cristina Pecile, Vanna Larizza, Lidia Int J Mol Sci Article Biallelic mutations in RECQL4 gene, a caretaker of the genome, cause Rothmund-Thomson type-II syndrome (RTS-II) and confer increased cancer risk if they damage the helicase domain. We describe five families exemplifying clinical and allelic heterogeneity of RTS-II, and report the effect of pathogenic RECQL4 variants by in silico predictions and transcripts analyses. Complete phenotype of patients #39 and #42 whose affected siblings developed osteosarcoma correlates with their c.[1048_1049del], c.[1878+32_1878+55del] and c.[1568G>C;1573delT], c.[3021_3022del] variants which damage the helicase domain. Literature survey highlights enrichment of these variants affecting the helicase domain in patients with cancer outcome raising the issue of strict oncological surveillance. Conversely, patients #29 and #19 have a mild phenotype and carry, respectively, the unreported homozygous c.3265G>T and c.3054A>G variants, both sparing the helicase domain. Finally, despite matching several criteria for RTS clinical diagnosis, patient #38 is heterozygous for c.2412_2414del; no pathogenic CNVs out of those evidenced by high-resolution CGH-array, emerged as contributors to her phenotype. MDPI 2018-04-06 /pmc/articles/PMC5979380/ /pubmed/29642415 http://dx.doi.org/10.3390/ijms19041103 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Colombo, Elisa A.
Locatelli, Andrea
Cubells Sánchez, Laura
Romeo, Sara
Elcioglu, Nursel H.
Maystadt, Isabelle
Esteve Martínez, Altea
Sironi, Alessandra
Fontana, Laura
Finelli, Palma
Gervasini, Cristina
Pecile, Vanna
Larizza, Lidia
Rothmund-Thomson Syndrome: Insights from New Patients on the Genetic Variability Underpinning Clinical Presentation and Cancer Outcome
title Rothmund-Thomson Syndrome: Insights from New Patients on the Genetic Variability Underpinning Clinical Presentation and Cancer Outcome
title_full Rothmund-Thomson Syndrome: Insights from New Patients on the Genetic Variability Underpinning Clinical Presentation and Cancer Outcome
title_fullStr Rothmund-Thomson Syndrome: Insights from New Patients on the Genetic Variability Underpinning Clinical Presentation and Cancer Outcome
title_full_unstemmed Rothmund-Thomson Syndrome: Insights from New Patients on the Genetic Variability Underpinning Clinical Presentation and Cancer Outcome
title_short Rothmund-Thomson Syndrome: Insights from New Patients on the Genetic Variability Underpinning Clinical Presentation and Cancer Outcome
title_sort rothmund-thomson syndrome: insights from new patients on the genetic variability underpinning clinical presentation and cancer outcome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979380/
https://www.ncbi.nlm.nih.gov/pubmed/29642415
http://dx.doi.org/10.3390/ijms19041103
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