Mutation Analysis Of GIGYF2 Gene

BackgroundParkinson disease(PD) is a group of most common neurodegenerative disorder.Clinically,the disease is characterized by a triad of rigidity,resting tremor and dyskinesia.The pathology feature of it is the formation of Lewy body in dopaminergic neurons of the brain.The onset age is usually over 60,and 1-2%of the patients are over 65-year old.The pathogenesis of PD is unclear yet. It may be related to genetic deficiency,oxidative stress and cytochondriome deficiency,stimulated acid toxicity,environmental toxicity,et al.About 10-15%of PD patients have a family history. As the development of molecular biology,genetic factor become a more and more important role in PD.Until now 15 chromosomal localizations are discovered to have linkage with PD,and 11 of them have been cloned,4 of which are AD(Autosomal dominant AD),and 6 of which are AR(Autosomal recesive AR),1 of which is related with late-onset PD.PARK11(2q36-37) was reported to be linkeged with PD in 2003.GIGYF2 gene,which is supposed to be a responsible gene of PD,owns a locus of 2q36.1 in PARK11.In the mutations analysis of GIGYF2 by Lautier C,7 mutations were discovered among Italian and French PD patients.The mutation frequency was 4.8%。In the following researches,some new mutations were discovered.However,there's still no conclusion about the relationship between GIGYF2 gene and PD through out all these researches yet.And no research on species other than Europeans and Americans has been carried on. ObjectiveEstablish a technical platform by using Polymerase Chain Reaction (PCR) and DNA sequencing to detect the mutations of GIGYF2 gene in Chinese patients with sporadic late-onset Parkinson's Disease,in order to make clear the mutation characteristics of GIGYF2 gene in Chinese PD patients.MethodsBy technology of PCR and DNA sequencing,mutation analysis of GIGYF2 gene in 300 unrelated Chinese patients with late-onset PD was performed.Then,mutation analysis was performed again of those exons with allele changes in 200 controls to decide whether they were mutations or polymorphism.ResultsBy DNA sequencing,we found 8 allele changes of GIGYF2 gene in 300 Chinese patients with sporadic late-onset PD,which were not found in DNA sequencing reports of the 200 controls.They are as follows: c.G766A,c.C1130A,c.C1417T,c.C1555T,c.GG1474-1475AA,c.C1738A, c.C2935T,c.G3208C。All of them were new mutations according to bdSNP data.The mutation frequency of GIGYF2 gene among Chinese Han patients with sporadic late onset PD is 2.7%。In our research we did not find any mutations which had been reported.Conclusion1 Establish GIGYF2 gene mutation diagnosis method by using DNA sequencing; 2 8 new mutations of GIGYF2 gene were discovered,which are as follows:c.G766A,c.C1130A,c.C1417T,c.C1555T,c.GG1474-1475AA, c.C1738A,c.C2935T,c.G3208C.The mutation frequency of GIGYF2 gene among Chinese Han patients with sporadic late-onset PD is 2.7%;3 The etiological mutations of GIGYF2 gene might be the etiological factors of Chinese sporadic late-onset PD.