Spectrum of rhodopsin mutations in Korean patients with retinitis pigmentosa

[摘要] Purpose: To determine the spectrum andfrequency of rhodopsin gene (RHO) mutations in Korean patientswith retinitis pigmentosa (RP) and to characterize genotype–phenotypecorrelations in patients with mutations. Methods: The RHO mutations werescreened by direct sequencing, and mutation prevalence was measured inpatients and controls. The impact of missense mutations to RP waspredicted by segregation analysis, peptide sequence alignment, and insilico analysis. The severity of disease in patients with the missensemutations was compared by visual acuity, electroretinography, opticalcoherence tomography, and kinetic visual field testing. Results: Five heterozygous mutationswere identified in six of 302 probands with RP, including a novelmutation (c.893C>A, p.A298D) and four known mutations (c.50C>T,p.T17M; c.533A>G, p.Y178C; c.888G>T, p.K296N; and c.1040C>T,p.P347L). The allele frequency of missense mutations was measured in114 ethnically matched controls. p.A298D, newly identified in asporadic patient, had never been found in controls and was predicted tobe pathogenic. Among the patients with the missense mutations, weobserved the most severe phenotype in patients with p.P347L, lesssevere phenotypes in patients with p.Y178C or p.A298D, and a relativelymoderate phenotype in a patient with p.T17M. Conclusions: The results reveal thespectrum of RHO mutations in Korean RP patients and clinicalfeatures that vary according to mutations. Our findings will be usefulfor understanding these genetic spectra and the genotype–phenotypecorrelations and will therefore help with predicting disease prognosisand facilitating the development of gene therapy.

[学科分类] 生物化学/生物物理