Cargando…
DJ-1 Mutations are Rare in a Swedish Parkinson Cohort
Mutations in the PARK7 gene, DJ-1, have been reported to cause early-onset and familial Parkinson’s disease (PD). The function of DJ-1 and how it contributes to the development of the disease is not clear today, but several studies report that DJ-1 is responsive to oxidative stress and important for...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Bentham Open
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083820/ https://www.ncbi.nlm.nih.gov/pubmed/21532868 http://dx.doi.org/10.2174/1874205X01105010008 |
_version_ | 1782202452209041408 |
---|---|
author | Anvret, Anna Blackinton, Jeff G Westerlund, Marie Ran, Caroline Sydow, Olof Willows, Thomas Håkansson, Anna Nissbrandt, Hans Belin, Andrea Carmine |
author_facet | Anvret, Anna Blackinton, Jeff G Westerlund, Marie Ran, Caroline Sydow, Olof Willows, Thomas Håkansson, Anna Nissbrandt, Hans Belin, Andrea Carmine |
author_sort | Anvret, Anna |
collection | PubMed |
description | Mutations in the PARK7 gene, DJ-1, have been reported to cause early-onset and familial Parkinson’s disease (PD). The function of DJ-1 and how it contributes to the development of the disease is not clear today, but several studies report that DJ-1 is responsive to oxidative stress and important for the maintenance of mitochondria. We have screened three coding regions of DJ-1 (exon 2, 5 and 7) in a Swedish Parkinson cohort. The Swedish PD material consisted of 67 patients with a self reported positive family history of PD and 77 patients with early-onset of disease (≤50 years old). We detected two patients with the previously reported synonymous mutation, Ala167Ala (c.501A>G, rs71653621), in exon 7. No Ala167Ala carriers were identified among 213 neurologically healthy Swedish controls. Mechanisms by which the synonymous Ala167Ala mutation can have consequences are unknown. It may affect the mRNA stability, secondary structure of mRNA, synthesis, turnover, protein folding and function. We could show a 1.3% decrease in DJ-1 mRNA folding energy in the A<G substituted sequence compared to the wild type sequence in silico, suggesting a possible small effect of Ala167Ala on DJ-1 gene function. This is the first report on an identified DJ-1 mutation in Swedish PD patients. Our results, in combination with those of previous studies, strengthen the hypothesis that alterations in DJ-1 are not a common cause of familial and early-onset PD world-wide. |
format | Text |
id | pubmed-3083820 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Bentham Open |
record_format | MEDLINE/PubMed |
spelling | pubmed-30838202011-04-29 DJ-1 Mutations are Rare in a Swedish Parkinson Cohort Anvret, Anna Blackinton, Jeff G Westerlund, Marie Ran, Caroline Sydow, Olof Willows, Thomas Håkansson, Anna Nissbrandt, Hans Belin, Andrea Carmine Open Neurol J Article Mutations in the PARK7 gene, DJ-1, have been reported to cause early-onset and familial Parkinson’s disease (PD). The function of DJ-1 and how it contributes to the development of the disease is not clear today, but several studies report that DJ-1 is responsive to oxidative stress and important for the maintenance of mitochondria. We have screened three coding regions of DJ-1 (exon 2, 5 and 7) in a Swedish Parkinson cohort. The Swedish PD material consisted of 67 patients with a self reported positive family history of PD and 77 patients with early-onset of disease (≤50 years old). We detected two patients with the previously reported synonymous mutation, Ala167Ala (c.501A>G, rs71653621), in exon 7. No Ala167Ala carriers were identified among 213 neurologically healthy Swedish controls. Mechanisms by which the synonymous Ala167Ala mutation can have consequences are unknown. It may affect the mRNA stability, secondary structure of mRNA, synthesis, turnover, protein folding and function. We could show a 1.3% decrease in DJ-1 mRNA folding energy in the A<G substituted sequence compared to the wild type sequence in silico, suggesting a possible small effect of Ala167Ala on DJ-1 gene function. This is the first report on an identified DJ-1 mutation in Swedish PD patients. Our results, in combination with those of previous studies, strengthen the hypothesis that alterations in DJ-1 are not a common cause of familial and early-onset PD world-wide. Bentham Open 2011-03-22 /pmc/articles/PMC3083820/ /pubmed/21532868 http://dx.doi.org/10.2174/1874205X01105010008 Text en © Anvret et al.; Licensee Bentham Open. http://creativecommons.org/licenses/by-nc/3.0/ This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited. |
spellingShingle | Article Anvret, Anna Blackinton, Jeff G Westerlund, Marie Ran, Caroline Sydow, Olof Willows, Thomas Håkansson, Anna Nissbrandt, Hans Belin, Andrea Carmine DJ-1 Mutations are Rare in a Swedish Parkinson Cohort |
title | DJ-1 Mutations are Rare in a Swedish Parkinson Cohort |
title_full | DJ-1 Mutations are Rare in a Swedish Parkinson Cohort |
title_fullStr | DJ-1 Mutations are Rare in a Swedish Parkinson Cohort |
title_full_unstemmed | DJ-1 Mutations are Rare in a Swedish Parkinson Cohort |
title_short | DJ-1 Mutations are Rare in a Swedish Parkinson Cohort |
title_sort | dj-1 mutations are rare in a swedish parkinson cohort |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083820/ https://www.ncbi.nlm.nih.gov/pubmed/21532868 http://dx.doi.org/10.2174/1874205X01105010008 |
work_keys_str_mv | AT anvretanna dj1mutationsarerareinaswedishparkinsoncohort AT blackintonjeffg dj1mutationsarerareinaswedishparkinsoncohort AT westerlundmarie dj1mutationsarerareinaswedishparkinsoncohort AT rancaroline dj1mutationsarerareinaswedishparkinsoncohort AT sydowolof dj1mutationsarerareinaswedishparkinsoncohort AT willowsthomas dj1mutationsarerareinaswedishparkinsoncohort AT hakanssonanna dj1mutationsarerareinaswedishparkinsoncohort AT nissbrandthans dj1mutationsarerareinaswedishparkinsoncohort AT belinandreacarmine dj1mutationsarerareinaswedishparkinsoncohort |