Molecular biology and Electrophysiology of Retinitis Pigmentosa

视网膜色素变性是一种视网膜光感受器的进行性变性。x连锁色素性视网膜炎（XLRP）是该疾病最严重的形式。我们在一个日本家族中发现了与x连锁视网膜色素变性相关的RPGR基因微缺失。缺失范围从外显子1到外显子11。患者症状严重，起病早，恶化快。通过PCR和直接测序筛选出RPGR基因外显子1-19、15a和ORF15，但DNA基因组外显子1-11无法扩增，其他外显子序列正常。Southern blot分析显示，RPGR中没有外显子4、8、10和11。我们扩增了缺失周围的片段，结果我们确定缺失的起点位于外显子1前79bp处，而终点位于外显子11下游42bp处。因此该缺失长度为30204bp，包含了RPGR基因的rcc1样结构域。我们的报道首次证实了RPGR微缺失在人类视网膜中跨越rcc1样结构域，有力地支持了RPGR的n端序列是人类视网膜中RPGR功能所必需的。我们的研究表明rcc1样结构域是RPGR的重要功能域。

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.