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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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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. |
format | Online Article Text |
id | pubmed-5979380 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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