Spectrum of rhodopsin mutations in Korean patients with retinitis pigmentosa
Spectrum of rhodopsin mutations in Korean patients with retinitis pigmentosa
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发表时间：
2011-04
期刊：
影响因子：
2.2
通讯作者：
Kwang Joong Kim;Cinoo Kim;J. Bok;Kyung-Seon Kim;Eun-Ju Lee;S. Park;Hum Chung;B. Han;Hyung-Lae Kim;K. Kimm;H. Yu;Jong-Young Lee
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作者：
Kwang Joong Kim;Cinoo Kim;J. Bok;Kyung-Seon Kim;Eun-Ju Lee;S. Park;Hum Chung;B. Han;Hyung-Lae Kim;K. Kimm;H. Yu;Jong-Young Lee
目的确定韩国视网膜色素变性（RP）患者视紫红质基因（RHO）突变的谱和频率，并描述突变患者的基因型-表型相关性。方法采用直接测序法筛查RHO基因突变，并测定患者和对照组的突变率。通过分离分析、肽序列比对和计算机模拟分析预测错义突变对RP的影响。通过视力、视网膜电图、光学相干断层扫描和动态视野检查比较错义突变患者的疾病严重程度。结果302例RP先证者中有6例存在5种杂合突变，包括1种新突变（c.893C>A，p.A298D）和4种已知突变（c.50C>T，p.T17M; c.533A>G，p.Y178C; c.888G>T，p.K296N; c.1040C>T，p.P347L）。在114名种族匹配的对照中测量了错义突变的等位基因频率。p.A298D，新发现的散发患者，从未发现在对照组中，并预测是致病性的。在有错义突变的患者中，我们观察到p.P347L患者的表型最严重，p.Y178C或p.A298D患者的表型不太严重，p.T17M患者的表型相对中等。结论该结果揭示了韩国RP患者的RHO突变谱和根据突变而变化的临床特征。我们的研究结果将有助于理解这些遗传谱和基因型-表型相关性，因此将有助于预测疾病预后和促进基因治疗的发展。
Purpose To determine the spectrum and frequency of rhodopsin gene (RHO) mutations in Korean patients with retinitis pigmentosa (RP) and to characterize genotype–phenotype correlations in patients with mutations. Methods The RHO mutations were screened by direct sequencing, and mutation prevalence was measured in patients and controls. The impact of missense mutations to RP was predicted by segregation analysis, peptide sequence alignment, and in silico analysis. The severity of disease in patients with the missense mutations was compared by visual acuity, electroretinography, optical coherence tomography, and kinetic visual field testing. Results Five heterozygous mutations were identified in six of 302 probands with RP, including a novel mutation (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 in 114 ethnically matched controls. p.A298D, newly identified in a sporadic patient, had never been found in controls and was predicted to be pathogenic. Among the patients with the missense mutations, we observed the most severe phenotype in patients with p.P347L, less severe phenotypes in patients with p.Y178C or p.A298D, and a relatively moderate phenotype in a patient with p.T17M. Conclusions The results reveal the spectrum of RHO mutations in Korean RP patients and clinical features that vary according to mutations. Our findings will be useful for understanding these genetic spectra and the genotype–phenotype correlations and will therefore help with predicting disease prognosis and facilitating the development of gene therapy.