Schwahn U, Lenzner S, Dong J, Feil S, Hinzmann B, van Duijnhoven G, Kirschner R, Hemberger M, Bergen A A, Rosenberg T, Pinckers A J, Fundele R, Rosenthal A, Cremers F P, Ropers H H, Berger W
Max-Planck-Institute for Molecular Genetics, Berlin (Dahlem), Germany.
Nat Genet. 1998 Aug;19(4):327-32. doi: 10.1038/1214.
X-linked retinitis pigmentosa (XLRP) results from mutations in at least two different loci, designated RP2 and RP3, located at Xp11.3 and Xp21.1, respectively. The RP3 gene was recently isolated by positional cloning, whereas the RP2 locus was mapped genetically to a 5-cM interval. We have screened this region for genomic rearrangements by the YAC representation hybridization (YRH) technique and detected a LINE1 (L1) insertion in one XLRP patient. The L1 retrotransposition occurred in an intron of a novel gene that consisted of five exons and encoded a polypeptide of 350 amino acids. Subsequently, nonsense, missense and frameshift mutations, as well as two small deletions, were identified in six additional patients. The predicted gene product shows homology with human cofactor C, a protein involved in the ultimate step of beta-tubulin folding. Our data provide evidence that mutations in this gene, designated RP2, are responsible for progressive retinal degeneration.
X连锁视网膜色素变性（XLRP）是由至少两个不同基因座的突变引起的，分别命名为RP2和RP3，位于Xp11.3和Xp21.1。RP3基因最近通过定位克隆分离出来，而RP2基因座通过遗传定位到一个5厘摩的区间。我们通过酵母人工染色体代表性杂交（YRH）技术筛选了该区域的基因组重排，并在一名XLRP患者中检测到一个LINE1（L1）插入。L1逆转座发生在一个由五个外显子组成的新基因的内含子中，该基因编码一个350个氨基酸的多肽。随后，在另外六名患者中鉴定出无义、错义、移码突变以及两个小缺失。预测的基因产物与人辅因子C具有同源性，人辅因子C是一种参与β-微管蛋白折叠最终步骤的蛋白质。我们的数据提供了证据，表明这个命名为RP2的基因中的突变是进行性视网膜变性的原因。
