Xiaoli Zhang, Weiling Fu, Pang Chi-Pui, Yeung Kwun-Yan
Center for Molecular Diagnosis and Gene Therapy, Affiliated South-west Hospital, Third Military Medical University, Chongqing 400038.
Chin Med Sci J. 2002 Dec;17(4):225-30.
To identify and evaluate mutations in the RP1 gene among Chinese patients with retinitis pigmentosa (RP).
Leukocyte DNA of 92 RP patients were collected in Hong Kong. Sequence changes of the entire coding region of the RP1 gene were examined using PCR, conformation sensitive gel electrophoresis and DNA sequencing.
In total, 1 nonsense mutation and 1 nonsense variant as well as 10 missense alterations were identified in the RP1 gene, among which, Arg677Ter was found in 1 RP patient and another nonsense variant, Arg1933Ter, was identified in 3 normal individuals and 1 patient with Stargardt's disease, suggesting its nonpathogenicity. Arg77Ter is expected to lead to large disruptions of the encoded protein.
The nonpathogenicity of Arg1933Ter indicates that the C-terminal 224 residues of RP1 protein may be not critical for RP1. The most C-terminal truncation previously reported was due to Tyr1053 (1-bp del) and occurred in RP patients. Thus RP can be caused by reduction in the level of the region of RP1 protein after codon 1052 but before 1933. To ascertain such a proposition, genotypes of more RP patients may reveal more RP causative mutations and more sequence alterations different than those of other ethnic groups.
鉴定和评估中国视网膜色素变性（RP）患者中RP1基因的突变情况。
收集了香港92例RP患者的白细胞DNA。采用聚合酶链反应（PCR）、构象敏感凝胶电泳和DNA测序技术检测RP1基因整个编码区的序列变化。
在RP1基因中总共鉴定出1个无义突变、1个无义变异以及10个错义改变，其中，在1例RP患者中发现了Arg677Ter，在3名正常个体和1例Stargardt病患者中鉴定出另一个无义变异Arg1933Ter，提示其无致病性。Arg77Ter预计会导致编码蛋白的大量破坏。
Arg1933Ter的无致病性表明RP1蛋白的C末端224个残基可能对RP1并不关键。先前报道的最末端截短是由于Tyr1053（1-bp缺失），发生在RP患者中。因此，RP可能是由RP1蛋白在密码子1052之后但在1933之前区域水平的降低引起的。为了确定这一观点，更多RP患者的基因型可能会揭示更多RP致病突变以及与其他种族不同的更多序列改变。
