一个新的 PRPF31 突变基因在一个具有常染色体显性遗传的视网膜色素变性和黄斑变性的中国大家族中被发现。
A novel PRPF31 mutation in a large Chinese family with autosomal dominant retinitis pigmentosa and macular degeneration.
机构信息
Center for Human Molecular Biology & Genetics, The Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China ; Sichuan Translational Research Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
出版信息
PLoS One. 2013 Nov 11;8(11):e78274. doi: 10.1371/journal.pone.0078274. eCollection 2013.
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.
目的
本研究旨在鉴定一个常染色体显性遗传的视网膜色素变性和黄斑变性的中国大家庭的致病基因。
方法
对该家族进行全基因组扫描分析，初步定位致病基因。对候选基因 PRPF31 进行单核苷酸多态性（SNP）的快照分析，进行两点 LOD 得分分析，以进行候选基因筛选。对候选基因 PRPF31 外显子进行测序，以确定突变。
结果
在 PRPF31 基因中发现了一个新的无义突变，是由插入引起的。该家系的 19 名 RP 患者均携带这种杂合性无义突变。该无义突变位于 PRPF31 基因外显子 9 上的 chr19：54629961-54629961，插入核苷酸“A”导致 snoRNA 结合域（NOP 域）中第 307 位密码子和第 322 位提前终止的移码。
结论
本报告首次将 PRPF31 基因的无义突变与 adRP 和 JMD 相关联。我们的研究结果表明，PRPF31 可以导致同一个家族中不同的临床表型，导致 adRP 或 adRP 和 JMD 的综合征。我们相信，我们在 PRPF31 的 chr19：54629961-54629961 外显子 9 中发现的新型“A”插入突变，可以为 adRP 和 JMD 的临床检测提供进一步的遗传证据。
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