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Specific Alu elements involved in a significant percentage of copy number variations of the STK11 gene in patients with Peutz–Jeghers syndrome

Peutz–Jeghers syndrome (PJS) is a rare hereditary syndrome characterized by the occurrence of hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmentation and increased risk of cancer in multiple internal organs. PJS is preconditioned by the manifestation of mutations in the STK11...

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Autores principales: Borun, Pawel, De Rosa, Marina, Nedoszytko, Boguslaw, Walkowiak, Jaroslaw, Plawski, Andrzej
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559094/
https://www.ncbi.nlm.nih.gov/pubmed/25841653
http://dx.doi.org/10.1007/s10689-015-9800-5
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author Borun, Pawel
De Rosa, Marina
Nedoszytko, Boguslaw
Walkowiak, Jaroslaw
Plawski, Andrzej
author_facet Borun, Pawel
De Rosa, Marina
Nedoszytko, Boguslaw
Walkowiak, Jaroslaw
Plawski, Andrzej
author_sort Borun, Pawel
collection PubMed
description Peutz–Jeghers syndrome (PJS) is a rare hereditary syndrome characterized by the occurrence of hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmentation and increased risk of cancer in multiple internal organs. PJS is preconditioned by the manifestation of mutations in the STK11 gene. The majority of detected STK11 changes are small scale mutations, however recent studies showed the significant contribution of medium-sized changes commonly known as copy number variations (CNVs). Here we present a novel 7001 bps deletion of STK11 gene fragment, in which we identified the presence of breakpoints (BPs) within the Alu elements. Comparative meta-analysis with the 80 other CNV cases from 12 publications describing STK11 mutations in patients with PJS revealed the participation of specific Alu elements in all deletions of exons 2–3 so far described. Moreover, we have shown their involvement in the two other CNVs, deletion of exon 2 and deletion of exon 1–3 respectively. Deletion of exons 2–3 of the STK11 gene may prove to be the most recurrent large rearrangement causing PJS. In addition, the sequences present in its BPs may be involved in a formation of a significant percentage of the remaining gene CNVs. This gives a new insight into the conditioning of this rare disease and enables improvements in PJS genetic diagnostics.
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spelling pubmed-45590942015-09-09 Specific Alu elements involved in a significant percentage of copy number variations of the STK11 gene in patients with Peutz–Jeghers syndrome Borun, Pawel De Rosa, Marina Nedoszytko, Boguslaw Walkowiak, Jaroslaw Plawski, Andrzej Fam Cancer Original Article Peutz–Jeghers syndrome (PJS) is a rare hereditary syndrome characterized by the occurrence of hamartomatous polyps in the gastrointestinal tract, mucocutaneous pigmentation and increased risk of cancer in multiple internal organs. PJS is preconditioned by the manifestation of mutations in the STK11 gene. The majority of detected STK11 changes are small scale mutations, however recent studies showed the significant contribution of medium-sized changes commonly known as copy number variations (CNVs). Here we present a novel 7001 bps deletion of STK11 gene fragment, in which we identified the presence of breakpoints (BPs) within the Alu elements. Comparative meta-analysis with the 80 other CNV cases from 12 publications describing STK11 mutations in patients with PJS revealed the participation of specific Alu elements in all deletions of exons 2–3 so far described. Moreover, we have shown their involvement in the two other CNVs, deletion of exon 2 and deletion of exon 1–3 respectively. Deletion of exons 2–3 of the STK11 gene may prove to be the most recurrent large rearrangement causing PJS. In addition, the sequences present in its BPs may be involved in a formation of a significant percentage of the remaining gene CNVs. This gives a new insight into the conditioning of this rare disease and enables improvements in PJS genetic diagnostics. Springer Netherlands 2015-04-05 2015 /pmc/articles/PMC4559094/ /pubmed/25841653 http://dx.doi.org/10.1007/s10689-015-9800-5 Text en © The Author(s) 2015 https://creativecommons.org/licenses/by/4.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Article
Borun, Pawel
De Rosa, Marina
Nedoszytko, Boguslaw
Walkowiak, Jaroslaw
Plawski, Andrzej
Specific Alu elements involved in a significant percentage of copy number variations of the STK11 gene in patients with Peutz–Jeghers syndrome
title Specific Alu elements involved in a significant percentage of copy number variations of the STK11 gene in patients with Peutz–Jeghers syndrome
title_full Specific Alu elements involved in a significant percentage of copy number variations of the STK11 gene in patients with Peutz–Jeghers syndrome
title_fullStr Specific Alu elements involved in a significant percentage of copy number variations of the STK11 gene in patients with Peutz–Jeghers syndrome
title_full_unstemmed Specific Alu elements involved in a significant percentage of copy number variations of the STK11 gene in patients with Peutz–Jeghers syndrome
title_short Specific Alu elements involved in a significant percentage of copy number variations of the STK11 gene in patients with Peutz–Jeghers syndrome
title_sort specific alu elements involved in a significant percentage of copy number variations of the stk11 gene in patients with peutz–jeghers syndrome
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559094/
https://www.ncbi.nlm.nih.gov/pubmed/25841653
http://dx.doi.org/10.1007/s10689-015-9800-5
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