Analysis of the RPGR gene in 11 pedigrees with the retinitis pigmentosa type 3 genotype: Paucity of mutations in the coding region but splice defects in two families
Analysis of the RPGR gene in 11 pedigrees with the retinitis pigmentosa type 3 genotype: Paucity of mutations in the coding region but splice defects in two families
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DOI：
10.1086/515523
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发表时间：
1997-09-01
影响因子：
9.8
通讯作者：
Swaroop, A
中科院分区：
文献类型：
--
作者：
Fujita, R;Buraczynska, M;Swaroop, A
X连锁色素性视网膜炎（XLRP）是一种严重的遗传性进行性视网膜变性。 Xp21.1 条状基因座下的 RP3（色素性视网膜炎类型 (3)）被认为是大多数 XLRP 家族中的疾病的原因。连锁分析和染色体缺失患者的鉴定已经精确了 RP3 基因座的位置，最近导致了 RPGR（色素性视网膜炎 GTP 酶调节因子）基因的克隆，该基因已被证明在 XLRP 家族中发生突变。 10%-15% XLRP 患者。为了系统地表征 RPGR 突变，我们通过单倍型分析鉴定了 11 个 III 型色素性视网膜炎 (RP3) 家族。对代表这些 RP3 家族的患者的 PCR 扩增基因组 DNA 进行序列分析，未发现 RPGR 外显子 2-19 中存在任何致病性突变（跨越超过 98% 的编码区）。在来自两个家庭的患者中，我们发现 剪接位点附近内含子区域的过渡突变（IVS10+3 和 IVS13-8）。 RNA 分析表明，两个剪接位点突变都会导致异常 RPGR 转录本的产生。我们的结果支持这样的假设：所报道的 RPGR 基因的突变并不是 XLRP RP3 亚型的常见缺陷，并且大多数致病突变可能存在于尚未鉴定的基因中。 RPGR 外显子或 Xp21.1 附近的另一个基因中。
X-linked retinitis pigmentosa (XLRP) is a severe form of inherited progressive retinal degeneration. The RP3 (retinitis pigmentosa type (3) under bar locus at Xp21.1 is believed to account for the disease in the majority of XLRP families. Linkage analysis and identification of patients with chromosomal deletion have refined the location of the RP3 locus and recently have led to the cloning of the RPGR (retinitis pigmentosa GTPase regulator) gene, which has been shown to be mutated in 10%-15% of XLRP patients. In order to systematically characterize the RPGR mutations, we identified 11 retinitis pigmentosa type III (RP3) families by haplotype analysis. Sequence analysis of the PCR-amplified genomic DNA from patients representing these RP3 families did not reveal any causative mutation in RPGR exons 2-19, spanning >98% of the coding region. In patients from two families, we identified transition mutations in the intron region near splice sites (IVS10+3 and IVS13-8). RNA analysis showed that both splice-site mutations resulted in the generation of aberrant RPGR transcripts. Our results support the hypothesis that mutations in the reported RPGR gene are not a common defect in the RP3 subtype of XLRP and that a majority of causative mutations may reside either in as yet unidentified RPGR exons or in another nearby gene at Xp21.1.