title: GIGYF2 mutation in late-onset Parkinson's disease with cognitive impairment.
abstract: Although in the last two decades there has been considerable progress in understanding the genetic basis of Parkinson's disease (PD), the majority of PD is sporadic and its genetic causes are largely unknown. In an attempt to identify novel genetic causes of PD, whole-exome sequencing and subsequent analyses were performed in a family featuring late-onset PD with cognitive impairment. A novel genetic variant (p.Arg610Gly) in the GIGYF2 gene, previously known to be associated with PD, was identified as potential disease-causing mutation. The GIGYF2 p.Arg610Gly mutation situated in the GYF domain of the encoding protein was predicted to be pathogenic and to disrupt the GYF's ligand-binding abilities. Although further research is still required, this finding may shed light on the GIGYF2-associated mechanisms that lead to PD and suggests insulin dysregulation as a disease-specific mechanism for both PD and cognitive dysfunction.
authors.affiliation: Biodonostia Research Institute, Neurosciences area, Gipuzkoa, Spain.|Department of Neurology, Hospital Universitario Donostia, Movement Disorders Unit, Guipuzcoa, Spain.|Centro de investigación biomédica en Red para enfermedades Neurodegenerativas (CIBERNED), Carlos III Health Institute, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ruiz-Martinez
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, USA.
authors.forename: Catharine E
authors.initials: CE
authors.lastname: Krebs
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Makarov
authors.affiliation: Biodonostia Research Institute, Neurosciences area, Gipuzkoa, Spain.|Department of Neurology, Hospital Universitario Donostia, Movement Disorders Unit, Guipuzcoa, Spain.|Centro de investigación biomédica en Red para enfermedades Neurodegenerativas (CIBERNED), Carlos III Health Institute, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Gorostidi
authors.affiliation: Biodonostia Research Institute, Neurosciences area, Gipuzkoa, Spain.|Department of Neurology, Hospital Universitario Donostia, Movement Disorders Unit, Guipuzcoa, Spain.|Centro de investigación biomédica en Red para enfermedades Neurodegenerativas (CIBERNED), Carlos III Health Institute, Madrid, Spain.|Department of Neurosciences, University of the Basque Country, EHU-UPV, Guipuzcoa, Spain.
authors.forename: Jose Félix
authors.initials: JF
authors.lastname: Martí-Massó
authors.affiliation: Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, USA.|Departments of Psychiatry, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, USA.|Friedman Brain and Mindich Child Health and Development Institutes, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, USA.
authors.forename: Coro
authors.initials: C
authors.lastname: Paisán-Ruiz
mesh_terms: D019943:Amino Acid Substitution; D002352:Carrier Proteins / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics* / Q000378:metabolism; D059472:Exome; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C478016:GIGYF2 protein, human