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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.

SUBMITTER: Ruiz-Martinez J

PROVIDER: S-EPMC4624020 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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GIGYF2 mutation in late-onset Parkinson's disease with cognitive impairment.

Ruiz-Martinez Javier J Krebs Catharine E CE Makarov Vladimir V Gorostidi Ana A Martí-Massó Jose Félix JF Paisán-Ruiz Coro C

Journal of human genetics 20150702 10

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 identif ...[more]

PMID: 26134514

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