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. 2019 Jan;34(1):133-137.
doi: 10.1002/mds.27559. Epub 2018 Dec 10.

Utility and implications of exome sequencing in early-onset Parkinson's disease

Joanne Trinh  1 , Katja Lohmann  1 , Hauke Baumann  1 , Alexander Balck  1   2 , Max Borsche  1   2 , Norbert Brüggemann  1   2 , Leon Dure  3 , Marissa Dean  3 , Jens Volkmann  4 , Sinem Tunc  1   2 , Jannik Prasuhn  1   2 , Heike Pawlack  1 , Sophie Imhoff  1 , Christina M Lill  1 , Meike Kasten  1   5 , Peter Bauer  6 , Arndt Rolfs  6   7 ; International Parkinson's Disease Genomics Consortium (IPDGC); Christine Klein  1
Affiliations

Utility and implications of exome sequencing in early-onset Parkinson's disease

Joanne Trinh et al. Mov Disord. 2019 Jan.

Abstract

Background: Although the genetic load is high in early-onset Parkinson's disease, thorough investigation of the genetic diagnostic yield has yet to be established. The objectives of this study were to assess variants in known genes for PD and other movement disorders and to find new candidates in 50 patients with early-onset PD.

Methods: We searched for variants either within genes listed by the International Parkinson and Movement Disorder Society Task Force on Genetic Nomenclature or rare homozygous variants in novel candidate genes. Further, exome data from 1148 European PD patients (International Parkinson Disease Genomics Consortium) were used for association testing.

Results: Seven patients (14%) carried pathogenic or likely pathogenic variants in Parkin, PLA2G6, or GBA. In addition, rare missense variants in DNAJC13:p.R1830C and in PPM1K:p.Y352C were detected. SPG7:p.A510V and PPM1K:p.Y352C revealed significant association with PD risk (P < 0.05).

Conclusions: Although we identified pathogenic variants in 14% of our early-onset PD patients, the majority remain unexplained, and novel candidates need to be validated independently to better further evaluate their role in PD. © 2018 International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; biomarker; lymphocyte activation gene-3.

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Conflict of interest statement

Relevant conflicts of interest/financial disclosures: The authors declare no conflict of interest.

Figures

FIG. 1.
FIG. 1.
Nominated novel pathogenic variants for EOPD. DNAJC13 p.R1830C (NM_015268, c.5488C>T) variant presents in affected mother (L-1452) and son (L-1451). (B) PPM1K homozygous p.Y352C (NM_152542, c.1055A>G) variant in eariy-onset patient. (C) Filtering criteria to identify novel candidates. AOO, age of onset; age, age of patient; GnomAD, genome aggregate consortium; ExAC, exome aggregate consortium; CADD, combined annotation dependent.
See this image and copyright information in PMC

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