Mutations Analysis Of NR2E3Gene In Chinese Patients With Retinitis Pigmentosa

Objective To identify the mutation profiles of the NR2E3gene in the patients withrentinitis pigmentosa (RP) in Ningxia Hui Autonomous Region and to evaluate their potentialinteraction in the pathogenesis of RP.Methods120individuals with RP were recruited for this study from October2009toNovember2010. Based on family history,33(18%) of the patients were classified as adRP,20(15%) as arRP, and67(67%) as simplex RP. The clinical features were determined bycomplete ophthalmologic examinations. Polymerase chain reaction (PCR) and direct DNAsequencing were used to screen in the entire coding region and splice sites of NR2E3gene.Association analysis was performed for sequence variants with the multivariate logisticregression analysis.Results A total of12different sequence variants in the NR2E3gene were identified,including6novel sequence variants. Five variants were detected in non-coding regions. Threevariants were synonymous changes. Three variants (p.Glu140Gly, p.Met163Thr andp.Val302Ile) were missense changes. All of them were NR2E3gene polymorphisms andshowed no positive correlation with RP. A missense change, p.Glu121Lys, was foundsimultaneously in one adRP patient of NXRP-1family, three sRP patients (4.0%) and2control subjects (2.0%). Further direct DNA sequencings were performed on other8affectedindividuals in this adRP family and the p.Glu121Lys variant was found in five affectedindividuals. Notably, total six affected individuals with the p.Glu121Lys variant showed severe RP phenotypes (early onset and early central visual impairment) than other3affectedindividuals without p.Glu121Lys variant.Conclusions In this study, NR2E3was not associated with RP in Ningxia population.The frequency of p.Glu121Lys in Ningxia RP patients was lower than previous reports inother populations. The p.Glu121Lys variant in NR2E3gene was not involved in thepathogenesis in this family with adRP, but it may be a modifier for RP.