Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Oct;60(10):637-40.
doi: 10.1038/jhg.2015.69. Epub 2015 Jul 2.

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

Javier Ruiz-Martinez  1   2   3 , Catharine E Krebs  4 , Vladimir Makarov  5 , Ana Gorostidi  1   2   3 , Jose Félix Martí-Massó  1   2   3   6 , Coro Paisán-Ruiz  4   7   8
Affiliations

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

Javier Ruiz-Martinez et al. J Hum Genet. 2015 Oct.

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.

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Due to the late-onset of the disease presentation, ranging from 78 to 88 years, and the early death of apparently unaffected parents (age of death: 72 and 43 years for father and mother, respectively), the pattern of inheritance in this family remains unknown. a) Pedigree structure of the family analyzed in this study. wt/m: heterozygous mutation carrier. WES was performed in individuals highlighted with a blue asterisk. b) GIGYF2 p.Arg610Gly mutation: Chromatogram sequences of wild-type (top) and mutant (bottom) sequences are shown on the right side, while conservation of the GIGYF2 p.Arg610Gly mutation in different species and GIGYF1 protein is shown on the left side. HS: Homo sapiens; CL: Canis lupus; BT: Bos taurus; MM: Mus musculus; DR: Danio rerio. c) GIGYF2 protein structure predicted by SMART (http://smart.embl-heidelberg.de/). The GYF domain consists of highly conserved glycine-tyrosine-phenylanine residues following the “GP[YF]xxxx[MV]xxWxxx[GN]YF” motif containing 60 amino-acid. The R610 amino-acid (highlighted in red) is the last residue of the GYF domain.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bonifati V. Genetics of Parkinson's disease--state of the art, 2013. Parkinsonism Relat Disord. 2013;20(Suppl 1):S23–S28. - PubMed
    1. Louis ED, Rios E, Applegate LM, Hernandez NC, Andrews HF. Jaw tremor: prevalence and clinical correlates in three essential tremor case samples. Mov Disord. 2006;21:1872–1878. - PubMed
    1. Krebs CE, et al. The Sac1 domain of SYNJ1 identified mutated in a family with early-onset progressive Parkinsonism with generalized seizures. Hum Mutat. 2013;34:1200–1207. - PMC - PubMed
    1. Exome Variant Server. NHLBI GO Exome Sequencing Project (ESP) Seattle, WA: 2015. (URL: http://evs.gs.washington.edu/EVS/) [April, 2015]
    1. Tan EK, Schapira AH. Summary of GIGYF2 studies in Parkinson's disease: the burden of proof. Eur J Neurol. 2009;17:175–176. - PubMed

Publication types

LinkOut - more resources