Bauer S, Fujita R, Buraczynska M, Abrahamson M, Ehinger B, Wu W, Falls T J, Andréasson S, Swaroop A
Department of Ophthalmology, University of Lund, Sweden.
Invest Ophthalmol Vis Sci. 1998 Nov;39(12):2470-4.
To assess the clinical phenotype in a Swedish family with X-linked retinitis pigmentosa (XLRP) resulting from a novel splice defect in the RPGR gene.
RPGR mutation analysis was performed in one family with XLRP, and several individuals from the family were examined clinically.
The causative mutation in the family was demonstrated to be a single base-pair change at the splice donor site in intron 7 that resulted in skipping of the complete exon 7 in the mature RPGR transcript. The aberrant mRNA is predicted to produce an RPGR protein with an in-frame deletion of 53 amino acids, corresponding to an RCC1-homology repeat. Clinical studies that included ophthalmological examination and full-field electroretinography showed that this splice mutation resulted in a comparatively less severe form of RP.
Correlation of a causative RPGR genotype with clinical findings in hemizygotes and carrier heterozygotes is an important step toward predictive diagnosis and should assist in the development of gene-based therapies in the future.
评估一个因RPGR基因出现新的剪接缺陷而导致X连锁视网膜色素变性（XLRP）的瑞典家族的临床表型。
对一个患有XLRP的家族进行RPGR突变分析，并对该家族的几名成员进行临床检查。
该家族的致病突变被证实是内含子7剪接供体位点的单个碱基对改变，导致成熟RPGR转录本中整个外显子7缺失。异常mRNA预计会产生一种RPGR蛋白，该蛋白在阅读框内缺失53个氨基酸，对应于一个RCC1同源重复序列。包括眼科检查和全视野视网膜电图在内的临床研究表明，这种剪接突变导致了相对较轻形式的视网膜色素变性（RP）。
将致病RPGR基因型与半合子和携带杂合子的临床发现相关联是迈向预测性诊断的重要一步，并且在未来应有助于基于基因的治疗方法的开发。
