Feng-Juan Gao1,2,3, Jian-Hong Dong4, Dan-Dan Wang1,2,3, Fang Chen5,6,7, Fang-Yuan Hu1,2,3, Qing Chang1,2,3, Ping Xu1,2,3, Wei Liu1,2,3, Jian-Kang Li5,8, Ying Huang1, Ji-Hong Wu1,2,3, Ge-Zhi Xu1,2,3. 1. Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai, China. 2. Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, China. 3. Key Laboratory of Myopia (Fudan University), Chinese Academy of Medical Sciences, National Health Commission, Shanghai, China. 4. Department of Ophthalmology, Central Hospital of Xuhui District, Shanghai, China. 5. BGI-Shenzhen, Shenzhen, China. 6. Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark. 7. Shenzhen Engineering Laboratory for Birth Defects Screening, BGI-Shenzhen, Shenzhen, China. 8. Department of Computer Science, City University of Hong Kong, Kowloon, Hong Kong SAR, China.
Abstract
PURPOSE: To provides the clinical and genetic characteristics of a series of Chinese patients with X-linked juvenile retinoschisis (XLRS) through multimodal imaging and next-generation sequencing. METHODS: Thirty patients (60 eyes) from 29 unrelated families of Chinese origin with XLRS were screened using multigene panel testing, and underwent a complete clinical evaluation. All variants identified in this study and reported in the Human Gene Mutation Database were analysed. RESULTS: Twenty-five distinct variants in the retinoschisin gene were identified, of which eight were novel, and one was de novo. Missense mutations were the most prevalent type, and mutation hot spot was localized in the discoidin domain. The mean Snellen best-corrected visual acuity was 0.28 ± 0.17. Of all eyes presenting with schisis, 92.86% had lamellar schisis and 62.5% had peripheral schisis. Schisis changes mostly involved inner and outer nuclear layers. X-linked juvenile retinoschisis (XLRS) patients had a high incidence of complications, and peripheral schisis was a risk factor for it. No obvious genotype-phenotype association was observed. CONCLUSION: This study provides comprehensive analyses of the genetic and clinical characteristics of XLRS in a cohort of Chinese patients. The fourth de novo mutation in RS1 was identified. And we show that XLRS has a wide spectrum of clinical characteristics; hence, molecular diagnosis is crucial for its diagnosis, differential diagnosis and genetic counselling. Peripheral schisis is a risk factor for the high incidence of complications, and no clear genotype-phenotype correlations were found.
PURPOSE: To provides the clinical and genetic characteristics of a series of Chinese patients with X-linked juvenile retinoschisis (XLRS) through multimodal imaging and next-generation sequencing. METHODS: Thirty patients (60 eyes) from 29 unrelated families of Chinese origin with XLRS were screened using multigene panel testing, and underwent a complete clinical evaluation. All variants identified in this study and reported in the Human Gene Mutation Database were analysed. RESULTS: Twenty-five distinct variants in the retinoschisin gene were identified, of which eight were novel, and one was de novo. Missense mutations were the most prevalent type, and mutation hot spot was localized in the discoidin domain. The mean Snellen best-corrected visual acuity was 0.28 ± 0.17. Of all eyes presenting with schisis, 92.86% had lamellar schisis and 62.5% had peripheral schisis. Schisis changes mostly involved inner and outer nuclear layers. X-linked juvenile retinoschisis (XLRS) patients had a high incidence of complications, and peripheral schisis was a risk factor for it. No obvious genotype-phenotype association was observed. CONCLUSION: This study provides comprehensive analyses of the genetic and clinical characteristics of XLRS in a cohort of Chinese patients. The fourth de novo mutation in RS1 was identified. And we show that XLRS has a wide spectrum of clinical characteristics; hence, molecular diagnosis is crucial for its diagnosis, differential diagnosis and genetic counselling. Peripheral schisis is a risk factor for the high incidence of complications, and no clear genotype-phenotype correlations were found.