title: Mutation analyses and association studies to assess the role of the presenilin-associated rhomboid-like gene in Parkinson's disease.
abstract: Presenilin-associated rhomboid-like (PARL), a serine protease located in the inner mitochondrial membrane, has been shown to genetically interact and process PTEN-induced putative kinase a protein known for its critical role in mitochondrial homeostasis and early-onset forms of Parkinson's disease (PD). The identification of a PD-associated variant in the PARL gene (p.Ser77Asn) led us to assess the relevance of PARL for PD pathogenesis using a mutation screening of the coding sequences and adjacent intronic sequences. We investigated 3 single nucleotide polymorphisms (rs3792589, rs13091, and rs3732581), a synonymous base substitution (Leu79Leu) and the previously described p.Ser77Asn mutation, which were subsequently screened in more than 2000 patients and controls. Not detecting the p.Ser77Asn mutation in our cohort, nor a robust association between variations in the PARL gene and PD, the role of disease causing genetic variants in the PARL gene could not be further substantiated in our samples. Our findings indicate that PARL mutations are a rare cause of PD and genetic variants are neither strong nor common risk factors in PD.
authors.affiliation: Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Tübingen, Germany; Department of Psychiatry and Psychotherapie, University Hospital Tübingen, Germany. Electronic address: richard.wuest@med.uni-tuebingen.de.
authors.forename: Richard
authors.initials: R
authors.lastname: Wüst
authors.affiliation: Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Tübingen, Germany; DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Maurer
authors.affiliation: Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Tübingen, Germany; DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Hauser
authors.affiliation: Department of Neurology, St Josef-Hospital, Ruhr-University Bochum, Bochum, Germany; Department of Neurology, Katholische Kliniken Ruhrhalbinsel GmbH, Essen.
authors.forename: Dirk
authors.initials: D
authors.lastname: Woitalla
authors.affiliation: Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Tübingen, Germany; DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany.
authors.forename: Manu
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, Tübingen, Germany; DZNE, German Center for Neurodegenerative Diseases, Tübingen, Germany; Clinical and Experimental Neurology, Luxembourg Center for Systems Biomedicine, University of Luxembourg, Luxembourg; Centre Hospitalier de Luxembourg, Luxembourg. Electronic address: rejko.krueger@uni.lu.
authors.forename: Rejko
authors.initials: R
authors.lastname: Krüger
mesh_terms: D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D006801:Humans; D008297:Male; D045726:Metalloproteases / Q000235:genetics* / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000502:physiology*; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D024101:Mitochondrial Proteins; D045726:Metalloproteases; C485223:PARL protein, human
keywords: PARL; PD genetic study; PINK1/Parkin pathway; Parkinson's disease