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

Joanne Trinh; Katja Lohmann; Hauke Baumann; Alexander Balck; Max Borsche; Norbert Brüggemann; Leon Dure; Marissa Dean; Jens Volkmann; Sinem Tunc; Jannik Prasuhn; Heike Pawlack; Sophie Imhoff; Christina M. Lill; Meike Kasten; Peter Bauer; Arndt Rolfs; Christine Klein

doi:10.1002/mds.27559

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

Joanne Trinh, Katja Lohmann, Hauke Baumann, Alexander Balck, Max Borsche, Norbert Brüggemann, Leon Dure, Marissa Dean, Jens Volkmann, Sinem Tunc, Jannik Prasuhn, Heike Pawlack, Sophie Imhoff, Christina M. Lill, Meike Kasten, Peter Bauer, Arndt Rolfs, Christine Klein^*

^*Corresponding author for this work

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.

Original language	English
Journal	Movement Disorders
Volume	34
Issue number	1
Pages (from-to)	133-137
Number of pages	5
ISSN	0885-3185
DOIs	https://doi.org/10.1002/mds.27559
Publication status	Published - 01.01.2019

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Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

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Trinh, J., Lohmann, K., Baumann, H., Balck, A., Borsche, M., Brüggemann, N., Dure, L., Dean, M., Volkmann, J., Tunc, S., Prasuhn, J., Pawlack, H., Imhoff, S., Lill, C. M., Kasten, M., Bauer, P., Rolfs, A., & Klein, C. (2019). Utility and implications of exome sequencing in early-onset Parkinson's disease. Movement Disorders, 34(1), 133-137. https://doi.org/10.1002/mds.27559

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title = "Utility and implications of exome sequencing in early-onset Parkinson's disease",

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. {\textcopyright} 2018 International Parkinson and Movement Disorder Society.",

author = "Joanne Trinh and Katja Lohmann and Hauke Baumann and Alexander Balck and Max Borsche and Norbert Br{\"u}ggemann and Leon Dure and Marissa Dean and Jens Volkmann and Sinem Tunc and Jannik Prasuhn and Heike Pawlack and Sophie Imhoff and Lill, {Christina M.} and Meike Kasten and Peter Bauer and Arndt Rolfs and Christine Klein",

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AU - Trinh, Joanne

AU - Lohmann, Katja

AU - Baumann, Hauke

AU - Balck, Alexander

AU - Borsche, Max

AU - Brüggemann, Norbert

AU - Dure, Leon

AU - Dean, Marissa

AU - Volkmann, Jens

AU - Tunc, Sinem

AU - Prasuhn, Jannik

AU - Pawlack, Heike

AU - Imhoff, Sophie

AU - Lill, Christina M.

AU - Kasten, Meike

AU - Bauer, Peter

AU - Rolfs, Arndt

AU - Klein, Christine

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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

Abstract

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