摘要
目的 研究视紫红质 (rhodopsin,RHO)基因在中国人视网膜色素变性 (retinitispigmentosa,RP)患者中的突变频率、特征及其在 RP发病机理中的作用。方法 运用构象敏感凝胶电泳和DNA直接测序方法对 10 0例香港地区中国籍 RP患者 RHO基因全编码区进行突变的筛选与检测。结果共发现 6种碱基变异 ,其中 3种为沉默型突变 ,两种为错义突变 ,1种为缺失突变。 P34 7L在 1例 5 5岁女性患者及其同样患 RP的 3名子女中检出。 P32 7(1- bp del)首次在 1例 5 3岁的晚发型 RP患者中发现 ,其 2 6岁的女儿同样携带该突变 ,但目前除眼底色素上皮出现斑点外 ,还没有 RP的任何症状。上述两种突变均未在对照组中发现。结论 10 0例 RP患者中检出两例携带 RHO基因突变 ,由此可预测香港地区约有 2 .0 %(95 %的可信区间为 0 .2 %～ 7.0 % )的 RP是由 RHO基因突变所致。 P34 7L突变改变了 RHO基因 C末端一段高度保守的氨基酸序列 ,致使视紫红质蛋白在细胞内的运输发生障碍。 P32 7(1bp del)使突变蛋白的羧基末端失去了原有的磷酸化位点及一段高度保守的功能区 ,其可能的致病机理有待在今后的研究中通过建立相应的转基因模型或细胞培养系统来阐明。
Objective To test the frequency and pattern of rhodopsin (RHO) mutations in Chinese retinitis pigmentosa (RP) patients and to evaluate their effects in the pathogenesis of RP. Methods Genomic DNA was extracted from peripheral blood samples of 100 Hong Kong Chinese RP patients. Sequence variants of the entire coding exons of the RHO gene were tested using PCR, conformation sensitive gel electrophoresis and DNA sequencing. Results Totally six nucleotide changes were identified, among which three were silent mutations, two missense mutations and one deletion mutation. P347L was found in one RP proband and her three children who also had RP. P327(1 bp del) was novel and detected in a late-onset RP patient of 53 years. Her 26-year-old daughter, also carrying the identified mutation, had no RP phenotypes except for the mottled retinal pigment epithelium (RPE) revealed by fundal examination. Neither of the two mutations was detected in normal controls. Conclusion Two patients had disease-causing mutations in the RHO gene, thus RHO mutations cause about 2.0% (95% confidence interval: 0 2%-7.0%) of all RP among Chinese in Hong Kong. A highly conserved C-terminal sequence QVS(A)PA was altered due to P347L and thereby resulting in an aberrant subcellular localization of rhodopsin. Loss of all six phosphorylatable residues at the C-terminus and the highly conserved C-terminal sequence QVS(A)PA may occur because of P327(1 bp del). To elucidate the predominant biochemical defects in such mutant, transgenic mice and transfected culture cells carrying P327(1 bp del) would be of greatest value.
出处
《中华医学遗传学杂志》
EI
CAS
CSCD
2002年第6期463-466,共4页
Chinese Journal of Medical Genetics
