Mutational hot spot within a new RPGR exon in X-linked retinitis pigmentosa
Mutational hot spot within a new RPGR exon in X-linked retinitis pigmentosa
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DOI：
10.1038/78182
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发表时间：
2000-08-01
期刊：
影响因子：
30.8
通讯作者：
Wright, AF
中科院分区：
文献类型：
--
作者：
Vervoort, R;Lennon, A;Wright, AF
基因RPGR先前在Xp21.1的RP 3区域中被鉴定，并且显示在10-20%的患有进行性视网膜变性X连锁视网膜色素变性（1，2）（XLRP）的患者中发生突变。这些突变主要影响与RCC 1同源的结构域，RCC 1是一种小GTdR Ran的鸟嘌呤核苷酸交换因子，尽管它们存在于低于连锁研究预测的70-75%的XLRP患者中（3-6）。如连锁研究预测的那样，在另外10-20%的XLRP患者中发现Xp11.3处的RP 2基因座突变（6-8）。因为在其余的XLRP患者的突变可能存在于未发现的外显子的RPGR，我们测序了172 kb的区域包含整个基因。序列分析揭示了一个新的3'末端外显子，该外显子在60%的XLRP患者中发生突变。该外显子编码567个氨基酸，具有富含谷氨酸残基的重复结构域。该序列在小鼠、牛和红鳍东方鲀基因中是保守的。它优先在小鼠和牛视网膜中表达，进一步支持了它对视网膜功能的重要性。我们的研究结果表明，RPGR的突变是RP 3型XLRP的唯一原因，并在超过70%的XLRP患者和估计11%的所有视网膜色素变性患者中占该疾病。
The gene RPGR was previously identified in the RP3 region of Xp21.1 and shown to be mutated in 10-20% of patients with the progressive retinal degeneration X-linked retinitis pigmentosa(1,2) (XLRP). The mutations predominantly affected a domain homologous to RCC1, a guanine nucleotide exchange factor for the small GTPase Ran, although they were present in fewer than the 70-75% of XLRP patients predicted from linkage studies(3-6) Mutations in the RP2 locus at Xp11.3 were found in a further 10-20% of XLRP patients, as predicted from linkage studies(6-8). Because the mutations in the remainder of the XLRP patients may reside in undiscovered exons of RPGR, we sequenced a 172-kb region containing the entire gene. Analysis of the sequence disclosed a new 3' terminal exon that was mutated in 60% of XLRP patients examined. This exon encodes 567 amino acids, with a repetitive domain rich in glutamic acid residues. The sequence is conserved in the mouse, bovine and Fugu rubripes genes. it is preferentially expressed in mouse and bovine retina, further supporting its importance for retinal function. Our results suggest that mutations in RPGR are the only cause of RP3 type XLRP and account for the disease in over 70% of XLRP patients and an estimated 11% of all retinitis pigmentosa patients.