Bowne Sara J, Sullivan Lori S, Gire Anisa I, Birch David G, Hughbanks-Wheaton Dianna, Heckenlively John R, Daiger Stephen P
The University of Texas Health Science Center, Human Genetics Center, School of Public Health, Houston, TX 77030, USA.
Mol Vis. 2008 May 19;14:922-7.
The purpose of this project was to determine if mutations, including large insertions or deletions, in the recently identified RP31 gene topoisomerase I-binding arginine-serine rich (RS) protein (TOPORS), cause an appreciable fraction of autosomal dominant retinitis pigmentosa (adRP).
An adRP cohort of 215 families was used to determine the frequency of TOPORS mutations. We looked for mutations in TOPORS by testing 89 probands from the cohort without mutations in other known adRP genes. Mutation detection was performed by fluorescent capillary sequencing and by multiplex ligation probe amplification.
Two different TOPORS mutations, p.Glu808X and p.Arg857GlyfsX9, were each identified in one proband. Patients with these mutations exhibited clinical signs typical of advanced adRP. No large deletions or insertions of TOPORS were identified in our study.
Point mutations and small insertions or deletions in TOPORS cause approximately 1% of adRP. Large deletions or insertions of TOPORS are not an appreciable cause of adRP. Contrary to previous reports, no distinct clinical phenotype was seen in these patients.
本项目的目的是确定最近鉴定出的RP31基因拓扑异构酶I结合富含精氨酸 - 丝氨酸（RS）蛋白（TOPORS）中的突变，包括大片段插入或缺失，是否导致相当一部分常染色体显性遗传性视网膜色素变性（adRP）。
使用一个包含215个家系的adRP队列来确定TOPORS突变的频率。我们通过检测该队列中89名先证者来寻找TOPORS中的突变，这些先证者在其他已知的adRP基因中没有突变。通过荧光毛细管测序和多重连接探针扩增进行突变检测。
在一名先证者中分别鉴定出两种不同的TOPORS突变，即p.Glu808X和p.Arg857GlyfsX9。具有这些突变的患者表现出晚期adRP的典型临床症状。在我们的研究中未发现TOPORS的大片段缺失或插入。
TOPORS中的点突变和小插入或缺失导致约1%的adRP。TOPORS的大片段缺失或插入不是adRP的明显病因。与先前的报道相反，这些患者未观察到明显的临床表型。
