Umeå University's logo

umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Low prevalence of known pathogenic mutations in dominant PD genes: A Swedish multicenter study
Show others and affiliations
2019 (English)In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 66, p. 158-165Article in journal (Refereed) Published
Abstract [en]

Objective: To determine the frequency of mutations known to cause autosomal dominant Parkinson disease (PD) in a series with more than 10% of Sweden's estimated number of PD patients.

Methods: The Swedish Parkinson Disease Genetics Network was formed as a national multicenter consortium of clinical researchers who together have access to DNA from a total of 2,206 PD patients; 85.4% were from population-based studies. Samples were analyzed centrally for known pathogenic mutations in SNCA (duplications/triplications, p.Ala30Pro, p.Ala53Thr) and LRRK2 (p.Asn1437His, p.Arg1441His, p.Tyr1699Cys, p.Gly2019Ser, p.Ile2020Thr). We compared the frequency of these mutations in Swedish patients with published PD series and the gnomAD database.

Results: A family history of PD in first- and/or second-degree relatives was reported by 21.6% of participants. Twelve patients (0.54%) carried LRRK2 p.(Gly2019Ser) mutations, one patient (0.045%) an SNCA duplication. The frequency of LRRK2 p.(Gly2019Ser) carriers was 0.11% in a matched Swedish control cohort and a similar 0.098% in total gnomAD, but there was a marked difference between ethnicities in gnomAD, with 42-fold higher frequency among Ashkenazi Jews than all others combined.

Conclusions: In relative terms, the LRRK2 p.(Gly2019Ser) variant is the most frequent mutation among Swedish or international PD patients, and in gnomAD. SNCA duplications were the second.most common of the mutations examined. In absolute terms, however, these known pathogenic variants in dominant PD genes are generally very rare and can only explain a minute fraction of familial aggregation of PD. Additional genetic and environmental mechanisms may explain the frequent co-occurrence of PD in close relatives.

Place, publisher, year, edition, pages
Elsevier, 2019. Vol. 66, p. 158-165
National Category
Medical Genetics
Identifiers
URN: urn:nbn:se:umu:diva-165118DOI: 10.1016/j.parkreldis.2019.07.032ISI: 000491684100026PubMedID: 31422003Scopus ID: 2-s2.0-85070555795OAI: oai:DiVA.org:umu-165118DiVA, id: diva2:1369359
Available from: 2019-11-11 Created: 2019-11-11 Last updated: 2023-03-24Bibliographically approved

Open Access in DiVA

fulltext(1104 kB)257 downloads
File information
File name FULLTEXT01.pdfFile size 1104 kBChecksum SHA-512
aa133ca7643be486edf672be745bff5ef63a1f63599be9b278543d560a49bf335e699237a9a1d00a2f93d934eb5a74d8d9c0598ee2ba1973e7ac9eaa2ce2c617
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMedScopus

Authority records

Linder, JanForsgren, Lars

Search in DiVA

By author/editor
Puschmann, AndreasHansson, OskarLinder, JanForsgren, Lars
By organisation
Clinical Neuroscience
In the same journal
Parkinsonism & Related Disorders
Medical Genetics

Search outside of DiVA

GoogleGoogle Scholar
Total: 257 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 380 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf