【摘要】 目的通过对国人X连锁遗传性视网膜劈裂症(XLRS)患者RS1基因突变分析,描述RS1基因突变特点和XLRS表型特征。设计回顾性病例系列。研究对象本实验室收集XLRS患者27例,其中12例家族史明确,15例为散发。方法利用PCR扩增DNA直接测序方法检测27例患者RS1基因6个编码外显子。并对所有患者行详细的眼科检查,包括矫正视力、裂隙灯显微镜查眼前节、散瞳后直接眼底镜查眼底及眼底照相、相干光断层扫描(OCT)和视网膜电图(ERG)。主要指标RS1基因基因突变,发病年龄,视力,眼底表现。结果在27例患者中检测到27种RS1基因突变,其中4种为新发现突变,22种位于第4-6外显子(85.2%),即RS1蛋白的盘状结构域。27种突变包括15种错义突变(55.6%),4种无义突变(14.8%),4种缺失或插入(14.8%),2种剪接位点改变(7.4%),2种大片段缺失(7.4%)。27例患者均为男性,平均发病年龄(4.70±1.25)岁(0~34岁)。平均最佳矫正视力(0.22±0.28)(手动~1.0)。27例患者(54眼)中,40眼黄斑劈裂(74.1%),7眼仅有周边视网膜劈裂,5眼黄斑萎缩(其中3眼合并周边视网膜劈裂)。结论本研究结果扩大了RS1基因突变谱,第4-6外显子区域是XLRS患者RS1基因突变的热突变区域,对怀疑为XRLS患者应先进行RS1基因第4-6外显子区域测序。更多还原

【Abstract】 Objective To identify the mutations of the RS1 gene in Chinese patients with X-linked retinoschisis(XLRS) and describe their associated phenotype. Design Retrospective cases series. Participants 27 patients including 12 patients with family history and 15 sporadic cases with retinolschisis were recruited. Methods All the exons including the exon-intron boundaries of the RS1 gene, were amplified by PCR and the products were analyzed by direct sequencing in all the patients, and each proband underwent clinical examinations, including best-corrected visual acuity(BCVA) using E decimal charts, slit-lamp biomicroscopy, fundus examination and photog raphy, optical coherence tomography(OCT),and electronic retinogram(ERG). Main Outcome Measures Mutations of RS1 gene, onset age, visual acuity, fundus appearances. Results 27 RS1 gene mutations were found in 27 unrelated families, 4 of which were novel and 22 of which were located in exon 4-6 that encodes the discoidin domain of RS1 gene(85.2%). The mutations contained 15 missence mutations(55.6%), 4 nonsense mutations(14.8%), 4 deletions/insertions(14.8%), 2 splice site mutations(7.4%), and 2 large genomic deletions(7.4%). All patients were males, the median age of onset was 4.70±1.25 years(rang 0-34 years), the median BCVA upon review was 0.22±0.289(rang hand motion-1.0). Of all the 27 patients(54 eyes), 40 eyes had typical macular schisis(74.1%), 7 eyes only had peripheral retinal schisis, 5 eyes had macular atrophy in which 3 had peripheral retinal schisis. Conclusion The mutations found in this study broaden the spectrum of RS1 gene mutations, and the exon 4-6 was the hot region of RS1 gene mutations, so these region should be given priority for RS1 gene mutation screening.更多还原