Mutations Analysis Of Retinitis Pigmentosa1Gene In Chinese Patients With Retinitis Pigmentosa

Objective Retinitis pigmentosa (RP) is a monogenic, inheritance blinding oculardisease. At present, there is no effective therapeutic method for RP. This study was to identifythe mutations of RP1gene in Chinese patients with RP in Ningxia Hui Autonomous Regionand to explore the potential interactions in the pathogenesis of RP.Methods The periphery blood of3-5ml was collected from110individuals with RP(35ADRP and75SRP) and100normal controls in Ningxia. Polymerase chain reaction (PCR)and direct DNA sequencing were used to screening the sequence alterations in the entirecoding region and splice sites of RP1gene. Multivariate analysis and two web-basedprograms (PolyPhen and SIFT) were used to analyze the results.Results A total of11sequence variants in RP1gene were identified, including2novelvariants (p.Lys1152Lys, c.*247A>C). Six variants (p.Gly706Arg, p.Arg872His, p.Asn985Tyr,p.Ala1670Thr, p.Ser1691Pro and p.Cys2033Tyr) were missense changes. Three variants(p.Gln1008Gln, p.Lys1152Lys and p.Gln1725Gln) were synonymous changes. Two variants(c.788-92T>C, c.*247A>C) were detected in non-coding regions. The frequency ofc.788-92T>C and c.*247A>C in RP patients were higher than in normal control (χ~2=9.12,χ~2=12.77; P<0.01). The c.*247A>C variant showed positive correlation with RP (r=1.11,P<0.05). Three SNPs (p.Arg872His, p.Ala1670Thr and p.Ser1691Pro) always coexist in the83RP patients. In normal control, p.Arg872His occurred in22persons, p.Ala1670Thr andp.Ser1691Pro coexisted in another36persons. The frequency of p.Arg872His, p.Ala1670Thrand p.Ser1691Pro in RP patients were higher than in normal control (P<0.01). By using web-based programs, p.Arg872His, p.Ala1670Thr and p.Ser1691Pro were predicted to be"Probably protective" with PolyPhen and to have protective effect for RP by SIFT. The onseton patients with three coexisting variants was (30.54±13.68) years, and the best correctedvisual acuity (BCVA) was0.50±0.38. The onset on patients without three coexisting variantswas (21.06±16.24) years, and the BCVA was0.40±0.33. There was a statistic significance onnyctalopia and BCVA between RP patients and normal control（t=2.01,t=2.11;P<0.05）Conclusions In this study, the prevalence of RP1mutations among the RP patients inNingxia population was lower than other populations (<1%). The c.*247A>C variant showedpositive correlation with RP. The coexisting SNPs (p.Arg872His, p.Ala1670Thr andp.Ser1691Pro) may play a protective role on RP patients and reduce the frequency ofdisease-causing mutatiaon on RP1gene.