FBXO7 gene mutations may be rare in Chinese early-onset Parkinsonism patients

Luo, Lin-zi; Xu, Qian; Guo, Jifeng; Wang, Lei; Shi, Changhe; Wei, Jiaohua; Long, Zhigao; Pan, Qian; Tang, Beisha; Xia, Kun; Yan, Xinxiang

doi:10.1016/j.neulet.2010.06.083

Cited by 12 publications

(14 citation statements)

References 19 publications

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“…Recently, two missense substitutions (p.Ile87Thr and p.Asp328Arg) were found in two EOPD patients in Taiwan [7]. We did not detect any mutation in our EOPD patients, which is compatible with the previous results of studies showing rare pathogenic mutations of the FBXO7 gene in typical PD patients of Chinese ethnicity [1], [7]. Nevertheless, our method using cDNA sequencing may miss some mutations in the non-coding and regulatory elements of the FBXO7 gene.…”

Section: Discussionsupporting

confidence: 90%

“…1A). The two reported [1] variants were confirmed using PCR-restriction fragment length polymorphism (RFLP) method (Fig. 1B).…”

Section: Resultsmentioning

confidence: 71%

“…Y52C AG genotype or G allele demonstrated a trend toward decrease in risk of developing PD (odds ratio: 0.33, 95% confidence interval: 0.09–0.95, p = 0.055–0.056). Analysis combining our patient and control subjects as well as the population in Luo's study [1] yielded results of statistically significant difference in genotype (0.9% vs. 2.8%, p = 0.012) and allele (0.5% vs. 1.4%, p = 0.012) distribution between patients and controls. The negative association of the Y52C AG genotype or G allele with PD was significant (odds ratio: 0.32–0.33, 95% confidence interval: 0.12–0.77, p = 0.016–0.017).…”

Section: Resultsmentioning

confidence: 90%

“…Two missense substitutions, p.Ile87Thr and p.Asp328Arg, in a single heterozygous state, were found in two EOPD patients in Taiwan [7]. Although no pathogenetic mutations in the FBXO7 gene were detected in 135 Chinese early-onset parkinsonism patients, the PD patients showed a trend toward decrease in Y52C G allele frequency compared with the controls [1].…”

Section: Introductionmentioning

confidence: 84%

“…There was a nominal difference in the Y52C G allele frequency between PD and controls ( p = 0.045). After combining data from China [1], significant difference in the Y52C G allele frequency between PD and controls ( p = 0.012) and significant association of G allele with decreased PD risk ( p = 0.017) can be demonstrated. Upon expressing EGFP-tagged Cys52 FBXO7 in cells, a significantly reduced rate of FBXO7 protein decay was observed when compared with cells expressing Tyr52 FBXO7.…”

mentioning

confidence: 98%

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FBXO7 Y52C Polymorphism as a Potential Protective Factor in Parkinson's Disease

Chen

Huang

et al. 2014

PLoS ONE

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Mutations in the F-box only protein 7 gene (FBXO7), the substrate-specifying subunit of SCF E3 ubiquitin ligase complex, cause Parkinson's disease (PD)-15 (PARK15). To identify new variants, we sequenced FBXO7 cDNA in 80 Taiwanese early onset PD patients (age at onset ≤50) and only two known variants, Y52C (c.155A>G) and M115I (c.345G>A), were found. To assess the association of Y52C and M115I with the risk of PD, we conducted a case–control study in a cohort of PD and ethnically matched controls. There was a nominal difference in the Y52C G allele frequency between PD and controls (p = 0.045). After combining data from China [1], significant difference in the Y52C G allele frequency between PD and controls (p = 0.012) and significant association of G allele with decreased PD risk (p = 0.017) can be demonstrated. Upon expressing EGFP-tagged Cys52 FBXO7 in cells, a significantly reduced rate of FBXO7 protein decay was observed when compared with cells expressing Tyr52 FBXO7. In silico modeling of Cys52 exhibited a more stable feature than Tyr52. In cells expressing Cys52 FBXO7, the level of TNF receptor-associated factor 2 (TRAF2) was significantly reduced. Moreover, Cys52 FBXO7 showed stronger interaction with TRAF2 and promoted TRAF2 ubiquitination, which may be responsible for the reduced TRAF2 expression in Cys52 cells. After induced differentiation, SH-SY5Y cells expressing Cys52 FBXO7 displayed increased neuronal outgrowth. We therefore hypothesize that Cys52 variant of FBXO7 may contribute to reduced PD susceptibility in Chinese.

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Section: Discussionsupporting

confidence: 90%

“…1A). The two reported [1] variants were confirmed using PCR-restriction fragment length polymorphism (RFLP) method (Fig. 1B).…”

Section: Resultsmentioning

confidence: 71%

Section: Resultsmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 84%

mentioning

confidence: 98%

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FBXO7 Y52C Polymorphism as a Potential Protective Factor in Parkinson's Disease

Chen

Huang

et al. 2014

PLoS ONE

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F-Box Only Protein 7 Gene in Parkinsonian-Pyramidal Disease

Deng¹,

Liang²,

Jankovic³

2013

JAMA Neurol

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arkinson disease is one of the most common neurodegenerative diseases associated with aging. At least 18 genetic loci and 13 disease-related genes for parkinsonism have been identified. Among them, PARK15-associated parkinsonism, also referred to as parkinsonianpyramidal disease (PPD), was found to be caused by mutations in the F-box only protein 7 gene (FBXO7). Parkinsonian-pyramidal disease differs from typical Parkinson disease chiefly by juvenile onset and the presence of spasticity. Four mutations have been identified and a pattern of autosomal recessive inheritance has been proposed in all reported PPD families. The FBXO7 protein is a member of the Skp1-Cullin-F-box-type E3 ubiquitin ligases, which play important roles in targeting proteins for ubiquitination. Although PPD is a relatively rare parkinsonian disorder, understanding its genetic and pathological mechanisms may lead to new insights into the pathogenesis of Parkinson disease and development of therapeutic strategies not only for PPD but also for other parkinsonian disorders.

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Genetics of Atypical Parkinsonism

Stamelou

Bhatia

2015

Movement Disorder Genetics

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FBXO7 gene mutations may be rare in Chinese early-onset Parkinsonism patients

Cited by 12 publications

References 19 publications

FBXO7 Y52C Polymorphism as a Potential Protective Factor in Parkinson's Disease

FBXO7 Y52C Polymorphism as a Potential Protective Factor in Parkinson's Disease

F-Box Only Protein 7 Gene in Parkinsonian-Pyramidal Disease

Genetics of Atypical Parkinsonism

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