Study On RP1 Gene Mutation In Chinese ADRP Patients And Assessment Of Local Retinal Function Of ADRP Patients With MfERG

Purpose:To survey the mutation spectrum of RP1 gene in Chinese autosomal dominant retinitis pigmentosa (RP) patients, to describe the multifocal ERGs changes in patients of RHO E334ter and patients of ADRP unrelated to RHO.Method:1. Clinical research:The inheritance patterns were determined according to the characteristics of the pedigrees. Clinical evaluations of patients include vision acuity, refractive status, slit-lamp examination with respect to the anterior segment, direct fundscopy, Humphery threshold perimetry and full-field ERG.2. Molecular hereditary research:A set of 17 probands from ADRP families and 55 sporadic RP patients who did not have mutations in the rhodopsin gene (based on previous work) formed the basis for the study. The single-strand conformation polymorphism(SSCP) method was used to search for RP1 gene sequence variants, which were then directly sequenced.3. Analysis of multifocal responses:Multifocal ERGs (mfERG) were recorded with the VERIS 4.2 systemfrom 5 patients of RHO E334ter and 6 ADRP patients who have mutations in other ADRP genes. The stimulus array consisted of 103 hexagons, and the total record time was approximately 4 minutes. The amplitudes and latent times of the first order kernels of different retinal areas were compared with those from 6 controls. The ratio of the amplitudes if the second- to first- order kernels were also caculated.Results:1. The polymorphism R872H of RP1 gene was detected in two ADRP families and two sporadic patients. Searched in a larger family, the CY family, we found all the patients were carrier of R872H. Chi-squared test shows that linkage disequilibrium exits between CY family and R872H(X2=6, p^O.05) .2. In the CY family there is considerable variation of the disease expression, the subjective onset of symptoms rang from 7 to more than 30 years of age. Night blindness is the first complain, and visual acuity decreased gradually. The patients show slight feather like opacity in the inferior posterior capsular membrane of the lens. Test with Humphrey 24-2 threshold program showed that the sensitivity decreases greatly. Rod and cone full-field ERGs were not detectable.3. With multifocal ERG we found:(1) . Patients of RHO E334ter showed multi-focal responses with prolonged latent time outside the central 7.5 degrees. Patients without mutations in RHO showed multi-focal responses with prolonged latent time outside the central 5 degrees. The amplitudes reduced all over the stimulus areas.(2) . No significant difference were found as compared the multifocal response from the temporal to the nasal retina and the superior to the inferior areas within the groups.(3) . The ratio of the amplitudes of the second- to first- order kernels reduced in the two patients groups.Conclusions:(1 ) . Linkage disequilibrium (LD) exits between CY family and RP1 gene R872HC X2=6, p 0.05 ), the exact pathogenic gene is likely located nearby RP1.(2) . In the research we detected 17 probands of ADRP families and 55sporadic RP patients and found 4 carriers of RP1 gene R872H, so it's occurrence in Chinese patients of ADRP is 11.8%.(3) . The patients in our study showed prolonged latent time outside thecentral 5-7.5 degree. The photoreceptor's density was reduced in the stimulus areas of RP patients. There is no difference between the two patient groups. The change of the second order kernel indicated that the inner retina is also involved, but the exact location need further research. We didn't find specific mfERG changes between different types of RP.