Summary of GIGYF2 studies in Parkinson’s disease: the burden of proof

Tan, Eng‐King; Schapira, Anthony H.V.

doi:10.1111/j.1468-1331.2009.02834.x

Cited by 16 publications

(13 citation statements)

References 16 publications

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“…However, several follow-up studies by others in various populations have failed to replicate the data, which raises considerable doubt on the causal role of GIGYF2 [184]. Notably, abrogation of GIGYF2 function in zebrafish neither result in a drastic cell loss in diencephalic dopaminergic neuron clusters nor render them more vulnerable to the toxicity of the parkinsonian neurotoxin MPTP [185].…”

Section: Other Familial Pd-linked Genes and Their Relevance To Sporadmentioning

confidence: 99%

Genetic Insights into Sporadic Parkinson's Disease Pathogenesis

Chai

Lim

2014

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Intensive research over the last 15 years has led to the identification of several autosomal recessive and dominant genes that cause familial Parkinson’s disease (PD). Importantly, the functional characterization of these genes has shed considerable insights into the molecular mechanisms underlying the etiology and pathogenesis of PD. Collectively; these studies implicate aberrant protein and mitochondrial homeostasis as key contributors to the development of PD, with oxidative stress likely acting as an important nexus between the two pathogenic events. Interestingly, recent genome-wide association studies (GWAS) have revealed variations in at least two of the identified familial PD genes (i.e. α-synuclein and LRRK2) as significant risk factors for the development of sporadic PD. At the same time, the studies also uncovered variability in novel alleles that is associated with increased risk for the disease. Additionally, in-silico meta-analyses of GWAS data have allowed major steps into the investigation of the roles of gene-gene and gene-environment interactions in sporadic PD. The emergent picture from the progress made thus far is that the etiology of sporadic PD is multi-factorial and presumably involves a complex interplay between a multitude of gene networks and the environment. Nonetheless, the biochemical pathways underlying familial and sporadic forms of PD are likely to be shared.

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Section: Other Familial Pd-linked Genes and Their Relevance To Sporadmentioning

confidence: 99%

Genetic Insights into Sporadic Parkinson's Disease Pathogenesis

Chai

Lim

2014

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“…Although four novel SNVs were identified present in the three affected individuals and absent in large number of control individuals (>10,000), including 188 ethnicity-matched control chromosomes, only one SNV, located in the GIGYF2 gene and not present in the Exome Aggregation Consortium (ExAc), was predicted to be pathogenic ( Table 1 ). Although the pathogenic role of GIGYF2 in PD remains controversial, 5 the GIGYF2 p.Arg610Gly mutation, which is situated in the GYF domain of the protein that is thought to possess ligand–binding properties, 6 was shown to be highly conserved across different species in both GIGYF1 and GIGYF2 proteins, and was predicted to disrupt the binding between the protein’s GYF domain and its interacting ligands (data not shown). The exon containing the p.Arg610Gly mutation was then sequenced in 107 Spanish PD patients, yielding no additional pathogenic mutation carriers; and the entire coding region of GIGYF2 was sequenced in 45 Spanish PD patients (AAO ranged from 61–81 years), leading to the identification of one novel mutation, p.Lys1006Gln_insQ, which is probably non-pathogenic as it lies within a highly polymorphic polyglutamine repeat, along with other already-reported, non-pathogenic mutations.…”

mentioning

confidence: 99%

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

et al. 2015

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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. While 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.

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“…[127] However, no disease-causing mutations were found in other European populations [128] and in recent months, over 10 replication studies have provided conflicting data, casting considerable doubt on the causal role of GIGYF2. [129] In addition, a pooled analysis of over 4,500 PD and 5,500 controls revealed that the estimated frequency of GIGYF2 mutations in the entire replication cohort was only about 0.001%. [127] Furthermore, the presence of mutations in healthy population controls or within asymptomatic family members of PD patients argues against causality even if longitudinal data are not available.…”

Section: Gigyf2mentioning

confidence: 99%

Clinicogenetics of Parkinson′s disease: A drawing but not completed picture

Wang¹,

Chan²

2014

Neuroimmunol Neuroinflammation

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Parkinson's disease (PD) is a prevalent neurodegenerative disorder mainly affecting the population over the age of 60 years. The past decade has seen rapidly emerging data supporting a major importance of genetic factors in the development of PD. Increasing number of large-scale and replicating association studies has facilitated the confirmation of the possible predisposing factors to PD and the selection of genetic variants for risk prediction. While evidences are accumulating that variations within the SNCA, LRRK2, MAPT and GBA genes increase the individuals' vulnerability to PD, inconclusive or negative results have been reported for an association between PD and variants of the parkin,

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Summary of GIGYF2 studies in Parkinson’s disease: the burden of proof

Cited by 16 publications

References 16 publications

Genetic Insights into Sporadic Parkinson's Disease Pathogenesis

Genetic Insights into Sporadic Parkinson's Disease Pathogenesis

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

Clinicogenetics of Parkinson′s disease: A drawing but not completed picture

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