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ESTABLISHING THE FBXO7 GENE SEQUENCING PROCEDURE IN EARLY-ONSET PARKINSON PATIENTS
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Abstract
Introduction: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, first described in 1817 by Dr. James Parkinson with the following characteristics: involuntary tremors, muscle weakness, hunched forward walking style. Recent studies have reported that FBXO7 gene is associated with with early-onset Parkinson's disease. Objective: To establish the genetic sequencing process to investigate FBXO7 variants among 20 Parkinson's patients in Vietnam. Methods: Genomic DNA from blood samples of Parkinson's patients were extracted, the primers for PCR amplification of all FBXO7 exons were designed and standardized. The Sanger sequencing process was developed to detect FBXO7 variants in 20 studied patients. Results: The PCR reactions amplifying all 9 exons of the FBXO7 gene were optimized, the Sanger sequencing process for these exons were also standardized. The heterozygous variants c.1493G>A (p.Arg498Gln) and c.587A>G (p.Asn196Ser) were detected in 2 patients. Another variant on the FBXO7 gene c.345G>A (p.Met115Ile) was detected in 5 other PD patients. Conclusion: The protocol for PCR and sequencing of all exons in FBXO7 gene was successfully developed. The primary results showed several variants of uncertain significance. Further studies are required to understand better the role of these variants in the pathogenesis of PD.
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2. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science. 1997 Jun 27;276(5321):2045–7.
3. Nelson DE, Randle SJ, Laman H. Beyond ubiquitination: the atypical functions of Fbxo7 and other F-box proteins. Open Biology. 2013 Oct;3(10):130131.
4. Yalcin-Cakmakli G, Olgiati S, Quadri M, Breedveld GJ, Cortelli P, Bonifati V, et al. A new Turkish family with homozygous FBXO7 truncating mutation and juvenile atypical parkinsonism. Parkinsonism Relat Disord. 2014 Nov;20(11):1248–52.
5. Shojaee S, Sina F, Banihosseini SS, Kazemi MH, Kalhor R, Shahidi GA, et al. Genome-wide linkage analysis of a Parkinsonian-pyramidal syndrome pedigree by 500 K SNP arrays. Am J Hum Genet. 2008 Jun;82(6):1375–84.
6. Di Fonzo A, Dekker MCJ, Montagna P, Baruzzi A, Yonova EH, Correia Guedes L, et al. FBXO7 mutations cause autosomal recessive, early-onset parkinsonian-pyramidal syndrome. Neurology. 2009 Jan 20;72(3):240–5.
7. Cenciarelli C, Chiaur DS, Guardavaccaro D, Parks W, Vidal M, Pagano M. Identification of a family of human F-box proteins. Curr Biol. 1999 Oct 21;9(20):1177–9.
8. Hsu JM, Lee YCG, Yu CTR, Huang CYF. Fbx7 functions in the SCF complex regulating Cdk1-cyclin B-phosphorylated hepatoma up-regulated protein (HURP) proteolysis by a proline-rich region. J Biol Chem. 2004 Jul 30;279(31):32592–602.