Cargando…

Genomic mechanisms underlying PARK2 large deletions identified in a cohort of patients with PD

OBJECTIVES: To identify the genomic mechanisms that result in PARK2 large gene deletions. METHODS: We conducted mutation screening using PCR amplification of PARK2-coding regions and exon-intron boundaries, followed by sequencing to evaluate a large series of 244 unrelated Portuguese patients with s...

Descripción completa

Detalles Bibliográficos
Autores principales: Morais, Sara, Bastos-Ferreira, Rita, Sequeiros, Jorge, Alonso, Isabel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856358/
https://www.ncbi.nlm.nih.gov/pubmed/27182553
http://dx.doi.org/10.1212/NXG.0000000000000073
_version_ 1782430494352211968
author Morais, Sara
Bastos-Ferreira, Rita
Sequeiros, Jorge
Alonso, Isabel
author_facet Morais, Sara
Bastos-Ferreira, Rita
Sequeiros, Jorge
Alonso, Isabel
author_sort Morais, Sara
collection PubMed
description OBJECTIVES: To identify the genomic mechanisms that result in PARK2 large gene deletions. METHODS: We conducted mutation screening using PCR amplification of PARK2-coding regions and exon-intron boundaries, followed by sequencing to evaluate a large series of 244 unrelated Portuguese patients with symptoms of Parkinson disease. For the detection of large gene rearrangements, we performed multiplex ligation-dependent probe amplification, followed by long-range PCR and sequencing to map deletion breakpoints. RESULTS: We identified biallelic pathogenic parkin mutations in 40 of the 244 patients. There were 18 different mutations, some of them novel. This study included mapping of 17 deletion breakpoints showing that nonhomologous end joining is the most common mechanism responsible for these gene rearrangements. None of these deletion breakpoints were previously described, and only one was present in 2 unrelated families, indicating that most of the deletions result from independent events. CONCLUSIONS: The c.155delA mutation is highly prevalent in the Portuguese population (62.5% of the cases). Large deletions were present in 42.5% of the patients. We present the largest study on the molecular mechanisms that mediate PARK2 deletions in a homogeneous population.
format Online
Article
Text
id pubmed-4856358
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Wolters Kluwer
record_format MEDLINE/PubMed
spelling pubmed-48563582016-05-13 Genomic mechanisms underlying PARK2 large deletions identified in a cohort of patients with PD Morais, Sara Bastos-Ferreira, Rita Sequeiros, Jorge Alonso, Isabel Neurol Genet Article OBJECTIVES: To identify the genomic mechanisms that result in PARK2 large gene deletions. METHODS: We conducted mutation screening using PCR amplification of PARK2-coding regions and exon-intron boundaries, followed by sequencing to evaluate a large series of 244 unrelated Portuguese patients with symptoms of Parkinson disease. For the detection of large gene rearrangements, we performed multiplex ligation-dependent probe amplification, followed by long-range PCR and sequencing to map deletion breakpoints. RESULTS: We identified biallelic pathogenic parkin mutations in 40 of the 244 patients. There were 18 different mutations, some of them novel. This study included mapping of 17 deletion breakpoints showing that nonhomologous end joining is the most common mechanism responsible for these gene rearrangements. None of these deletion breakpoints were previously described, and only one was present in 2 unrelated families, indicating that most of the deletions result from independent events. CONCLUSIONS: The c.155delA mutation is highly prevalent in the Portuguese population (62.5% of the cases). Large deletions were present in 42.5% of the patients. We present the largest study on the molecular mechanisms that mediate PARK2 deletions in a homogeneous population. Wolters Kluwer 2016-05-03 /pmc/articles/PMC4856358/ /pubmed/27182553 http://dx.doi.org/10.1212/NXG.0000000000000073 Text en © 2016 American Academy of Neurology This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
spellingShingle Article
Morais, Sara
Bastos-Ferreira, Rita
Sequeiros, Jorge
Alonso, Isabel
Genomic mechanisms underlying PARK2 large deletions identified in a cohort of patients with PD
title Genomic mechanisms underlying PARK2 large deletions identified in a cohort of patients with PD
title_full Genomic mechanisms underlying PARK2 large deletions identified in a cohort of patients with PD
title_fullStr Genomic mechanisms underlying PARK2 large deletions identified in a cohort of patients with PD
title_full_unstemmed Genomic mechanisms underlying PARK2 large deletions identified in a cohort of patients with PD
title_short Genomic mechanisms underlying PARK2 large deletions identified in a cohort of patients with PD
title_sort genomic mechanisms underlying park2 large deletions identified in a cohort of patients with pd
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856358/
https://www.ncbi.nlm.nih.gov/pubmed/27182553
http://dx.doi.org/10.1212/NXG.0000000000000073
work_keys_str_mv AT moraissara genomicmechanismsunderlyingpark2largedeletionsidentifiedinacohortofpatientswithpd
AT bastosferreirarita genomicmechanismsunderlyingpark2largedeletionsidentifiedinacohortofpatientswithpd
AT sequeirosjorge genomicmechanismsunderlyingpark2largedeletionsidentifiedinacohortofpatientswithpd
AT alonsoisabel genomicmechanismsunderlyingpark2largedeletionsidentifiedinacohortofpatientswithpd