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

Autor:	Wang HQ; Department of Ophthalmology, the Second People's Hospital of Quzhou, Quzhou 324022, Zhejiang Province, China., Cong PK; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, Zhejiang Province, China., He T; Department of Ophthalmology, Children's Hospital of Hangzhou, Hangzhou 310005, Zhejiang Province, China., Yu XF; Department of Ophthalmology, the Second People's Hospital of Quzhou, Quzhou 324022, Zhejiang Province, China., Huo YN; Department of Ophthalmology, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310020, Zhejiang Province, China.
Jazyk:	angličtina
Zdroj:	International journal of ophthalmology [Int J Ophthalmol] 2023 Oct 18; Vol. 16 (10), pp. 1595-1600. Date of Electronic Publication: 2023 Oct 18 (Print Publication: 2023).
DOI:	10.18240/ijo.2023.10.06
Abstrakt:	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-year-old 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. (International Journal of Ophthalmology Press.)
Databáze:	MEDLINE
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