Chiang S W Y, Wang D Y, Chan W M, Tam P O S, Chong K K L, Lam D S C, Pang C P
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Eye (Lond). 2006 May;20(5):602-5. doi: 10.1038/sj.eye.6701944.
More than 20 mutations associated with retinitis pigmentosa (RP) have been identified in the retinitis pigmentosa 1 (RP1) gene, all of them leading to the production of a truncated protein without 50-70% of the C-terminal of the RP1 protein. RP1 was recently found to be a microtubule-associated protein (MAP) and responsible for the organisation of the photoreceptor outer segment. The N-terminal doublecortin (DCX) domain of RP1 is essential for its function. But how the C-terminal of the protein affects its function is still not known. This study aims to get a better understanding of the RP1 gene by mutation screening on RP patients.
Peripheral blood was taken from 72 RP patients. Together with 101 RP patients and 190 control subjects previously reported, mutation screening was performed by polymerase chain reaction (PCR) and direct sequencing. Statistical analysis was performed using SPSS.
Two novel missense sequence changes, D984G and C727W, and one novel variant, 6492T>G, at the 3' untranslated region were found. They were not found in 190 control subjects. D984G causes RP. It creates two possible N-myristoylation sites according to PROSITE. C727W does not segregate with RP in the family. It abolishes an N-myristoylation site. R872H, a previously reported polymorphism, was predominantly present in control subjects (P=0.001).
Our results suggest that disruption of the C-terminal of RP1 may be associated with the development of RP, and the possible involvement of the RP1 polypeptide downstream of its DCX domain in normal RP1 function.
在视网膜色素变性1（RP1）基因中已鉴定出20多种与视网膜色素变性（RP）相关的突变，所有这些突变都会导致产生一种截短的蛋白质，该蛋白质缺少RP1蛋白C末端的50 - 70%。最近发现RP1是一种微管相关蛋白（MAP），并负责光感受器外段的组织。RP1的N末端双皮质素（DCX）结构域对其功能至关重要。但该蛋白质的C末端如何影响其功能仍不清楚。本研究旨在通过对RP患者进行突变筛查，更好地了解RP1基因。
采集72例RP患者的外周血。与之前报道的101例RP患者和190例对照受试者一起，通过聚合酶链反应（PCR）和直接测序进行突变筛查。使用SPSS进行统计分析。
在3'非翻译区发现了两个新的错义序列变化，D984G和C727W，以及一个新的变异6492T>G。在190例对照受试者中未发现这些变化。D984G导致RP。根据PROSITE，它产生了两个可能的N - 肉豆蔻酰化位点。C727W在家族中与RP不连锁。它消除了一个N - 肉豆蔻酰化位点。R872H，一种先前报道的多态性，主要存在于对照受试者中（P = 0.001）。
我们的结果表明，RP1 C末端的破坏可能与RP的发生有关，并且其DCX结构域下游的RP1多肽可能参与正常的RP1功能。
