先天性视网膜劈裂症基因突变型与临床表现型的关系  

Association of clinical features of X linked juvenile retinoschisis with new mutations in XLRS1 gene in Chinese families

作　　者：马翔[1] 黎晓新[2] 赵贵阳[1] 

机构地区：[1]大连医科大学第一医院眼科,116011 [2]北京大学人民医院眼科中心,100044

出　　处：《中华实验眼科杂志》2011年第4期367-372,共6页Chinese Journal Of Experimental Ophthalmology

基　　金：国家自然科学基金项目（30471859）

摘　　要：背景研究表明，导致先天性视网膜劈裂症（XLRS）的原因是RS1基因突变，XLRS的不同临床表现型与不同的基因突变类型有关，但基因型与表现型的关系仍不十分清楚。目的研究12个中国人XLRS家系及检测到的11种XLRS!基因突变与临床表现型的关系。方法对12个XLRS家系的28例男性患者（其余3例已死亡）及女性携带者和正常对照者分别进行详细的眼科检查，包括视力、屈光度、裂隙灯及眼底检查，部分患者行全视野视网膜电图（ERG）、眼底血管造影、光学相干断层扫描（OCT）及A／B型超声检查。采用聚合酶链反应（PCR）和单链构象多态性（SSCP）分析，对XLRSl基因突变进行筛查，并对发现异常泳带的PCR产物进行DNA测序，以明确突变位点及突变类型。结果12个家系的28例男性患者中27例有典型的黄斑及视网膜劈裂表现，ERG检查可见b波振幅下降，b／a波比值倒置。12个家系中检出11种不同的XLRSl致病基因突变，其中有4种新发现的基因突变，即：位于外显子1的移码突变（L9CfsX20）；位于外显子5的Aspl45His，Argl56Gly和Trp163X突变，并新发现1种非疾病相关多态性（NSP），即位于外显子6的576C—T（Pr0192Pro）改变。同时发现位于外显子1的移码突变（22de／T），外显子1与内含子1剪接位点突变（IVS1＋2TtoC）和Argl02Gln，Arg209His，Arg213Gln突变家系的患者，临床表现为严重型XLRS。结论XLRS1基因突变是导致中国人先天性视网膜劈裂的原因，XLRS的严重临床表现与基因突变的类型及突变位点具有一定的相关性。Background The main cause of X linked juvenile retinoschisis is mutation of RS1 gene. The phenotype of X linked juvenile retinoschisis is associated with the mutation types of RS1 gene. However, the relationship of genotype and phenotype of X linked juvenile retinoschisis is unclear. Objective The present study was to survey the clinical phenotype of X-linked juvenile retinoschisis in twelve Chinese families with eleven different mutations in the XLRS1 gene. Methods Complete ophthalmic examinations with slit lamp biomicroscopy, fundus examination and photography were carried out in 28 affected males. Ganzfeld electroretinography （ERG）, fundus fluorescein angiography,A and B-scan standardized echography and optical coherence tomography （OCT） were also performed in some patients. The coding regions of the XLRSI gene that encodes retinoschisin were amplified by polymerase chain reaction（PCR） and analyzed by the single strand conformation polymorphism（SSCP） assay. The RSI gene mutations were determined by direct sequencing in an automated sequencer. Written informed consent wasobtained prior to the survey. Results The 28 affected males showed a typical foveal schisis with or without peripheral retinoschisis. The typical response to white single flash ERG was seen with a reduction of the b-wave amplitude and a relative preservation of the a-wave amplitude ,causing a reduced b/a ratio in the male patients. A total of eleven different XLRS1 mutations in 12 families were identified, four of these mutations, including one frameshift mutation（22 del T） of exon 1,Asp145His,Arg156Gly and Trp163X mutations of exon 5, were first described in this survey. One non-disease-related polymorphism（NSP） ,or the 576C to T（Pro192Pro） change of exon 6 was also newly reported herein. In the families with a frameshift（22 del T） mutation of exon 1, a splice donor site mutation （IVS1 ＋2Tto C） and families with Argl02Gln, Arg209His and Arg213Gln mutations, a more severe retinoschisis clinical outcome was

关 键 词：先天性视网膜劈裂症 XLRS1基因 基因突变 基因型 表现型 

分 类 号：R774.1[医药卫生—眼科]