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WES-Based Screening of a Swedish Patient Series with Parkinson’s Disease

Kafantari, Efthymia LU ; Atterling Brolin, Kajsa LU orcid ; Wallenius, Joel LU orcid ; Swanberg, Maria LU and Puschmann, Andreas LU orcid (2025) In Genes 16(12).
Abstract

Background/Objective: Genetic factors contribute significantly to Parkinson’s disease (PD), especially in cases with early onset or positive family history. However, previous investigations of the genetic landscape in PD populations were mainly based on targeted genotyping. The aim of this study was to investigate the prevalence of pathogenic variants in known PD-associated genes in a series of Swedish PD patients. Methods: We performed whole-exome sequencing on 285 PD probands from southern Sweden. Our series was enriched for patients with early disease onset or positive family history. We focused on 44 genes previously linked to PD. Results: We identified a CHCHD2 p.(Phe84LeufsTer6) frameshift variant in two unrelated patients and... (More)

Background/Objective: Genetic factors contribute significantly to Parkinson’s disease (PD), especially in cases with early onset or positive family history. However, previous investigations of the genetic landscape in PD populations were mainly based on targeted genotyping. The aim of this study was to investigate the prevalence of pathogenic variants in known PD-associated genes in a series of Swedish PD patients. Methods: We performed whole-exome sequencing on 285 PD probands from southern Sweden. Our series was enriched for patients with early disease onset or positive family history. We focused on 44 genes previously linked to PD. Results: We identified a CHCHD2 p.(Phe84LeufsTer6) frameshift variant in two unrelated patients and report the first PD case of Swedish ancestry carrying the VPS35 p.(Asp620Asn) variant. Additionally, in one patient each, we found an SNCA duplication, an SNCA p.(Ala53Thr) variant, and a LRRK2 p.(Gly2019Ser) variant. Thus, only 2.1% (n = 6) of patients in this series had Mendelian monogenic PD forms. In addition, forty-three patients carried variants in GBA1, including T369M, which may lack disease-association in our population (n = 12); E326K (n = 22), which is classified as a PD risk variant; as well as N370S (n = 3), R329H (n = 3), S107L (n = 1), and L444P (n = 1), with one patient harboring both T369M and E326K. Pathogenic variants in ARSA, ATP7B, and PRKN genes were also detected in heterozygote form, but their role in PD remains uncertain. Conclusions: Monogenic forms of PD are rare in southern Sweden, even among the familial and early-onset PD patients that were overrepresented in our study. Our findings highlight the genetic diversity in Swedish PD patients and identify key variants for further functional and clinical studies.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
genetic investigation, Parkinson’s disease, whole-exome sequencing
in
Genes
volume
16
issue
12
article number
1482
publisher
MDPI AG
external identifiers
  • scopus:105026164842
  • pmid:41465155
ISSN
2073-4425
DOI
10.3390/genes16121482
language
English
LU publication?
yes
id
43842b6e-212e-40c4-afe9-b8cd068e80db
date added to LUP
2026-02-11 13:16:29
date last changed
2026-05-07 02:48:43
@article{43842b6e-212e-40c4-afe9-b8cd068e80db,
  abstract     = {{<p>Background/Objective: Genetic factors contribute significantly to Parkinson’s disease (PD), especially in cases with early onset or positive family history. However, previous investigations of the genetic landscape in PD populations were mainly based on targeted genotyping. The aim of this study was to investigate the prevalence of pathogenic variants in known PD-associated genes in a series of Swedish PD patients. Methods: We performed whole-exome sequencing on 285 PD probands from southern Sweden. Our series was enriched for patients with early disease onset or positive family history. We focused on 44 genes previously linked to PD. Results: We identified a CHCHD2 p.(Phe84LeufsTer6) frameshift variant in two unrelated patients and report the first PD case of Swedish ancestry carrying the VPS35 p.(Asp620Asn) variant. Additionally, in one patient each, we found an SNCA duplication, an SNCA p.(Ala53Thr) variant, and a LRRK2 p.(Gly2019Ser) variant. Thus, only 2.1% (n = 6) of patients in this series had Mendelian monogenic PD forms. In addition, forty-three patients carried variants in GBA1, including T369M, which may lack disease-association in our population (n = 12); E326K (n = 22), which is classified as a PD risk variant; as well as N370S (n = 3), R329H (n = 3), S107L (n = 1), and L444P (n = 1), with one patient harboring both T369M and E326K. Pathogenic variants in ARSA, ATP7B, and PRKN genes were also detected in heterozygote form, but their role in PD remains uncertain. Conclusions: Monogenic forms of PD are rare in southern Sweden, even among the familial and early-onset PD patients that were overrepresented in our study. Our findings highlight the genetic diversity in Swedish PD patients and identify key variants for further functional and clinical studies.</p>}},
  author       = {{Kafantari, Efthymia and Atterling Brolin, Kajsa and Wallenius, Joel and Swanberg, Maria and Puschmann, Andreas}},
  issn         = {{2073-4425}},
  keywords     = {{genetic investigation; Parkinson’s disease; whole-exome sequencing}},
  language     = {{eng}},
  number       = {{12}},
  publisher    = {{MDPI AG}},
  series       = {{Genes}},
  title        = {{WES-Based Screening of a Swedish Patient Series with Parkinson’s Disease}},
  url          = {{http://dx.doi.org/10.3390/genes16121482}},
  doi          = {{10.3390/genes16121482}},
  volume       = {{16}},
  year         = {{2025}},
}