A Novel Missense SNRNP200 Mutation Associated with Autosomal Dominant Retinitis Pigmentosa in a Chinese Family

作者：Liu, Tiecheng^*; Jin, Xin; Zhang, Xuemin; Yuan, Huijun; Cheng, Jing; Lee, Janet; Zhang, Baoquan; Zhang, Maonian; Wu, Jing; Wang, Lijuan; Tian, Geng; Wang, Weifeng

来源：PLos One, 2012, 7(9): e45464.

DOI：10.1371/journal.pone.0045464

• PROTEIN
• GENE
• PRPF31

The SNRNP200 gene encodes hBrr2, a helicase essential for pre-mRNA splicing. Six mutations in SNRNP200 have recently been discovered to be associated with autosomal dominant retinitis pigmentosa (adRP). In this work, we analyzed a Chinese family with adRP and identified a novel missense mutation in SNRNP200. To identify the genetic defect in this family, exome of the proband was captured and sequencing analysis was performed to exclude known genetic defects and find possible pathogenic mutations. Subsequently, candidate mutations were validated in affected family members using Sanger sequencing. A novel missense mutation, c.2653C>G transition (p.Q885E), in exon 20 of SNRNP200 was identified. The mutation co-segregated with the disease phenotype over four generations and was absent in 100 normal unaffected individuals. This mutation occurs at highly conserved position in hBrr2 and is predicted to have a functional impact, suggesting that hBrr2-dependent small nuclear riboproteins (snRNPs) unwinding and spliceosome activation is important in the pathogenesis of some variants of RP.

• 出版日期2012-9-19
• 单位深圳华大生命科学研究院; 中国人民解放军总医院