Molecular biology and Electrophysiology of Retinitis Pigmentosa

视网膜色素变性是视网膜光感受器的进行性变性。X连锁视网膜色素变性（XLRP）是最严重的形式的疾病。我们在一个日本家族中发现了X连锁视网膜色素变性的RPGR基因微缺失。缺失跨越外显子1至外显子11。患者起病早，病情恶化快，症状重。用PCR和直接测序法对RPGR基因的外显子1-19、15 a和ORF 15进行了筛选，但基因组的外显子1-11未能扩增出，其余外显子序列正常。Southern杂交显示RPGR中没有外显子4、8、10和11。我们对缺失片段周围的片段进行了扩增，确定了缺失起始点位于外显子1前79 bp处，终止点位于外显子11后42 bp处。因此，该缺失跨越30204 bp，从而终止了RPGR基因的RCC 1样结构域。我们的报告是第一个表明RPGR微缺失跨越RCC 1样结构域在人类，它强烈支持RPGR的N端序列是必需的RPGR在人类视网膜中的功能。我们的研究表明RCC 1样结构域是RPGR的重要功能。

Retinitis pigmentosa is a progressive degeneration of the retinal photoreceptors. X-linked retinitis pigmentosa (XLRP) is the most severe form of the disease. We identified a microdeletion in RPGR gene with X-linked retinitis pigmentosa in one Japanese family. The deletion spans exon 1 to exon 11. Patients had severe symptom with early onset and rapid deterioration. Exon 1-19, 15a and ORF15 of the RPGR gene was screened by PCR and direct sequence, however exon 1-11 of the DNA genome couldn't be amplified while other exons have normal sequence. Southern blot analysis revealed no exons 4, 8, 10 and 11 in RPGR. We amplified the fragments around the deletion, as a result, we ensure the deletion start-point is located in 79bp in front of exon 1, whereas end-point is 42bp downstream of exon 11. So the deletion spans 30204bp which comprehends the RCC1-like domain of RPGR gene. Our report is the first one which shows that the RPGR microdeletion spans RCC1-like domain in human, and that it strongly supports that the N-terminal sequence of RPGR is necessary for the function of RPGR in the human retina. Our research suggested that RCC1-like domain is the function essential to RPGR.