Spectrum of mutations in the RPGR gene that are identified in 20% of families with X-linked retinitis pigmentosa
Spectrum of mutations in the RPGR gene that are identified in 20% of families with X-linked retinitis pigmentosa
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DOI：
10.1086/301646
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发表时间：
1997-12-01
影响因子：
9.8
通讯作者：
Swaroop, A
中科院分区：
文献类型：
--
作者：
Buraczynska, M;Wu, WP;Swaroop, A
RP 3的RPGR（视网膜色素变性GTlymphocytosa regulator）基因是X连锁视网膜色素变性（XLRP）最常见的遗传亚型，已显示在10%-15%的欧洲XLRP患者中发生突变。我们已经检查了RPGR基因突变的80个受影响的男性从明显无关的XLRP家庭的队列，通过直接测序的PCR扩增产物的基因组DNA。在80个家族中的17个中鉴定出15种不同的推定致病突变;这些突变包括4种无义突变、1种错义突变、6种微缺失和4种导致剪接缺陷的内含子序列取代。大多数突变在RPGR蛋白的保守N-末端区域中检测到，所述区域含有与RCC-1蛋白（Ran-GTdR的鸟嘌呤核苷酸交换因子）中存在的那些同源的串联重复。我们的研究结果表明，突变无论是在RPGR基因或在位于其附近的另一个基因的序列尚未表征可能是一个更常见的原因XLRP。报告的研究将有利于建立基因型-表型相关性，并应导致进一步的调查，以寻求了解疾病的发病机制。
The RPGR (retinitis pigmentosa GTPase regulator) gene for RP3, the most frequent genetic subtype of X-linked retinitis pigmentosa (XLRP), has been shown to be mutated in 10%-15% of European XLRP patients. We have examined the RPGR gene for mutations in a cohort of 80 affected males from apparently unrelated XLRP families, by direct sequencing of the PCR-amplified products from the genomic DNA. Fifteen different putative disease-causing mutations were identified in 17 of the 80 families; these include four nonsense mutations, one missense mutation, six microdeletions, and four intronic-sequence substitutions resulting in splice defects. Most of the mutations were detected in the conserved N-terminal region of the RPGR protein, containing tandem repeats homologous to those present in the RCC-1 protein (a guanine nucleotide-exchange factor for Ran-GTPase). Our results indicate that mutations either in as yet uncharacterized sequences of the RPGR gene or in another gene located in its vicinity may be a more frequent cause of XLRP. The reported studies will be beneficial in establishing genotype-phenotype correlations and should lead to further investigations seeking to understand the mechanism of disease pathogenesis.