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Haoyu Chen, Xiaoqiang Xiao, Zhun Zhang, Yingjie Cao, Yuqian Zheng; Novel mutations in PRPF31 cause autosomal dominant retinitis pigmentosa identified by whole exome sequencing. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2771.
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© ARVO (1962-2015); The Authors (2016-present)
Retinitis pigmentosa (RP) is a genetically heterogeneous disease characterized by degeneration of photoreceptor and retinal pigment epithelium. Although many genetic mutations have been identified, these mutations count for only 60% of RP. The purpose of this study is to explore the genetic causes in three Chinese RP patients.
Three families with RP underwent a comprehensive ophthalmic examination. Blood samples of the RP patients and healthy control were obtained from these three families and used for DNA extraction. Genomic DNA was then sent for whole-exome capture followed by sequencing. The whole exome was captured using Agilent Sure Select Human All Exon Kit according to the manufacturer’s instructions. HiSeq 2500 platform was used for paired-end sequencing with read lengths of 100 bp and average coverage depth of at least 100× for each sample. After filtering against 1000 Genomes Project, 1000G_ASN, esp6500si_all, and dbSNP137, variants were verified in the remaining family members by PCR amplification and Sanger sequencing. The impaired protein function was predicted by on line software. The structure and express of this protein were analyzed by PDB and Genepaint database.
All the affected subjects in the three pedigrees were diagnosed with RP. Through whole exome sequencing (WES) and thereafter confirmation with PCR-Sanger sequence,thetwo frameshift mutations c.547del G (p.E183fs ),c.804del G (p.L268fs ) occurring at RP-F1 and RP-F2 family and a stopgain mutation c.1060C>T(p.R354X) occurring at RP-F3 family in the Pre-MRNA Processing Factor 31(PRPF31) gene were identified in the three families, respectively. The mutations were co-segregated within the pedigrees. These mutations showed impaired functions to its protein. Referring to the second and three dimensional structure model of PRPF31 protein shows the two frameshift mutations locate at the RNA binding domain of PRPF31 protein and the stopgain mutationp.R354X locates at the NLS domain, thus might change its the nuclear localization.The results of genepaint show PRPF31 highly express in most tissues.
Through WES, we identified two novel mutations,c.547del G (p.E183fs ),c.804del G (p.L268fs ) and a recurrent mutation c.1060C>T (p.R354X),in PRPF31 in three Chinese pedigrees.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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