A novel PRPF31 mutation in a large Chinese family with autosomal dominant retinitis pigmentosa and macular degeneration.
A novel PRPF31 mutation in a large Chinese family with autosomal dominant retinitis pigmentosa and macular degeneration.
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一个患有常染色体显性遗传性色素性视网膜炎和黄斑变性的中国大家族中的新 PRPF31 突变
DOI：
10.1371/journal.pone.0078274
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yang Z
中科院分区：
文献类型：
--
作者：
Lu F;Huang L;Lei C;Sha G;Zheng H;Liu X;Yang J;Shi Y;Lin Y;Gong B;Zhu X;Ma S;Qiao L;Lin H;Cheng J;Yang Z
目的研究一个常染色体显性遗传视网膜色素变性和黄斑变性家系的致病基因。方法对该家系进行基因组扫描分析，初步定位致病基因。用于候选基因过滤器的两点LOD得分分析的所选SNP的快照分析。对候选基因PRPF 31进行全外显子测序，以鉴定突变。结果在PRPF 31基因中发现了一个新的无义突变。1085家系19例RP患者均携带该杂合无义突变。无义突变位于PRPF 31基因外显子9的chr 19：54629961-54629961处，插入核苷酸“A”，其产生编码蛋白从p.307移码和snoRNA结合结构域（NOP结构域）中p.322处的早期终止。结论本研究首次将PRPF 31基因无义突变与adRP和JMD联系起来。我们的研究结果表明，PRPF 31可以导致不同的临床表型在同一个家庭中，无论是在adRP或adRP和JMD综合征。我们认为PRPF 31基因第9外显子chr 19：54629961-54629961处新的“A”插入突变的鉴定可为adRP和JMD的临床检测提供进一步的遗传学证据。
Purpose This study was intended to identify the disease causing genes in a large Chinese family with autosomal dominant retinitis pigmentosa and macular degeneration. Methods A genome scan analysis was conducted in this family for disease gene preliminary mapping. Snapshot analysis of selected SNPs for two-point LOD score analysis for candidate gene filter. Candidate gene PRPF31 whole exons' sequencing was executed to identify mutations. Results A novel nonsense mutation caused by an insertion was found in PRPF31 gene. All the 19 RP patients in 1085 family are carrying this heterozygous nonsense mutation. The nonsense mutation is in PRPF31 gene exon9 at chr19:54629961-54629961, inserting nucleotide “A” that generates the coding protein frame shift from p.307 and early termination at p.322 in the snoRNA binding domain (NOP domain). Conclusion This report is the first to associate PRPF31 gene's nonsense mutation and adRP and JMD. Our findings revealed that PRPF31 can lead to different clinical phenotypes in the same family, resulting either in adRP or syndrome of adRP and JMD. We believe our identification of the novel “A” insertion mutation in exon9 at chr19:54629961-54629961 in PRPF31 can provide further genetic evidence for clinical test for adRP and JMD.
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影响因子：
4.4
作者：
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通讯作者：
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通讯作者：
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作者：
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通讯作者：
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