A novel pathogenic splicing mutation of RPGR in a Chinese family with X-linked retinitis pigmentosa verified by minigene splicing assay  

作　　者：Hui-Qin Wang Pei-Kuan Cong Tian He Xiao-Feng Yu Ya-Nan Huo 

机构地区：[1]Department of Ophthalmology,the Second People’s Hospital of Quzhou,Quzhou 324022,Zhejiang Province,China [2]Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province,School of Life Sciences,Westlake University,Hangzhou 310024,Zhejiang Province,China [3]Department of Ophthalmology,Children’s Hospital of Hangzhou,Hangzhou 310005,Zhejiang Province,China [4]Department of Ophthalmology,the Second Affiliated Hospital of Zhejiang University School of Medicine,Hangzhou 310020,Zhejiang Province,China

出　　处：《International Journal of Ophthalmology(English edition)》2023年第10期1595-1600,共6页国际眼科杂志（英文版）

基　　金：Supported by National Natural Science Foundation of China(No.31751003);Natural Science Foundation of Zhejiang Province(No.LY20H120009);Health Commission of Zhejiang Province(No.2022KY168);Beijing Bethune Charitable Foundation(No.BJ-GY2021013J).

摘　　要：AIM:To report a novel splicing mutation in the RPGR gene(encoding retinitis pigmentosa GTPase regulator)in a three-generation Chinese family with X-linked retinitis pigmentosa(XLRP).METHODS:Comprehensive ophthalmic examinations including best corrected visual acuity,fundus photography,vision field,and pattern-visual evoked potential were performed to identify the disease phenotype of a six-yearold boy from the family(proband).Genomic DNA was extracted from peripheral blood of five available members of the pedigree.Whole-exome sequencing(WES),Sanger sequencing,and pSPL3-based exon trapping were used to investigate the aberrant splicing of RPGR.Human Splice Finder v3.1 and NNSPLICE v0.9 were used for in silico prediction of splice site variants.RESULTS:The proband was diagnosed as having retinitis pigmentosa(RP).He had severe symptoms with early onset.A novel splicing mutation,c.619+1G>C in RPGR was identified in the proband by WES and in four family members by Sanger sequencing.Minigene splicing assays verified that c.619+1G>C in RPGR would result in the formation of a damaging alternative transcript in which the last 91 bp of exon 6 were skipped,leading to the subsequent deletion of 623 correct amino acids(c.529_619del p.Val177Glnfs*16).CONCLUSION:We identify a novel splice donor site mutation causing aberrant splicing of RPGR.Our findings add to the catalog of pathological mutations of RPGR and further emphasize the functional importance of RPGR in RP pathogenesis and its complex clinical phenotypes.

关 键 词：retinitis pigmentosa X-linked inheritance RPGR splicing mutation pSPL3 minigene assay 

分 类 号：R774.11[医药卫生—眼科]