中国遗传性视网膜劈裂症患者临床特征及RS1基因突变筛查

  目的  探讨中国遗传性视网膜劈裂症(X-linked retinoschisis, XLRS)患者的临床特征及致病基因突变位点。  方法  研究纳入北京协和医院眼科经临床确诊的5个XLRS家系(包含12例患者)、10例散发病例、16名女性携带者和100名无眼疾的正常对照者。5个家系的先证者及10例散发病例(共15例患者)接受了详细的眼科检查。采集22例患者及16名携带者的外周静脉血3 ml用于提取基因组DNA。采用聚合酶链反应法对RS1基因的6个外显子片段进行扩增后直接测序, 以明确突变位点及突变类型。  结果  RS1基因检测共发现11种致病性突变, 包括p.E72K、p.W92C、p.R102Q、p.W112X、p.S134P、p.R156G、p.P193S、p.R200H、p.R209C、p.R213W和p.R213Q, 其中p.W112X和p.S134P突变为新发突变。1例散发病例未确定RS1基因突变位点。在确定突变的所有患者中, 5个家系的先证者和9例散发患者主诉均为不同程度的视力下降, 最佳矫正视力在0.04~0.8之间。眼底检查均存在特征性黄斑区劈裂, 其中有6例患者合并周边视网膜劈裂。携带RS1基因突变的患者中有10例接受视网膜电图检查, 结果显示9例患者的混合反应均呈特征性的负波形。携带同一致病性突变的不同患者病情轻重程度有所不同。  结论  XLRS患者在临床表型上存在较大差异, 未观察到基因型与表型间的相关性。

Clinical Characteristics and Genetic Mutations of Chinese Patients with X-linked Retinoschisis

Objective To assess the clinical features and to identify genetic mutations in Chinese patients with X-linked retinosChisis （XLRS）. Methods Patients were recruited from ophthalmic clinics in Peking Union Medical College Hospital. A cohort of five unrelated XLRS families （including 12 XLRS patients）, 10 sporadic XLRS patients, 16 female carriers and 100 normal subjects were enrolled in this study. Clinical evaluation was performed on all probands from 5 unrelated families and 10 sporadic cases involved in this study （ 15 patients in total）. Genomic DNA was extracted from the peripheral leukocytes of 22 patients and 16 carriers. All exons and the flanking introns of the RS 1 gene were amplified by polymerase chain reaction and screened for mutations by direct DNA sequencing. Results A total of 11 mutations including p. E72K, p. W92C, p. R102Q, p. W112X, p. S134P, p. R156G, p. P193S, p. R200H, p. R209C, p. R213W and p. R213Q were identified, among which p. WI12X and p. S134P were two novel mutations. We did not find any mutation in one sporadic case. Clinical evaluation on patients with RS1 mutation （ 14 patients in total） showed that reduced visual acuity was the common initial symptom in all 14 patients. The best corrected visual acuity ranged from 0. 04 to 0. 8. Typical foveal schi- sis was found in all 14 patients, among whom 6 were found to be with peripheral schisis. Electroretinogram was carried out on 10 patients with RS1 gene mutations and 9 of them displayed electronegative in the standard com- bined response. Patients with same RS1 mutation exhibited remarkable phenotypic differences. Conclusions Chinese patients with XLRS displayed variability in clinical phenotypes. No association was found between the genotypes and phenotypes.