Chen Zhixuan, Chen Jieqiong, Gao Min, Liu Yang, Wu Yidong, Wang Yafang, Gong Yuanyuan, Yu Suqin, Liu Wenjia, Wan Xiaoling, Sun Xiaodong
Department of Ophthalmology, School of Medicine, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, Shanghai, China.
Department of Ophthalmology, National Clinical Research Center for Eye Diseases, Shanghai, China.
Hum Mutat. 2022 Dec;43(12):2279-2294. doi: 10.1002/humu.24494. Epub 2022 Nov 9.
Retinitis pigmentosa (RP) is a monogenic disease characterized by irreversible degeneration of the retina. PRPF31, the second most common causative gene of autosomal dominant RP, frequently harbors copy number variations (CNVs), but the underlying mechanism is unclear. In this study, we summarized the phenotypic and genotypic characteristics of 18 RP families (F01-F18) with variants in PRPF31. The prevalence of PRPF31 variants in our cohort of Chinese RP families was 1.7% (18/1024). Seventeen different variants in PRPF31 were detected, including eight novel variants. Notably, four novel CNVs encompassing PRPF31, with a proportion of 22.2% (4/18), were validated to harbor gross deletions involving Alu/Alu-mediated rearrangements (AAMRs) in the same orientation. Among a total of 12 CNVs of PRPF31 with breakpoints mapped on nucleotide-resolution, 10 variants (83.3%) were presumably mediated by Alu elements. Furthermore, we described the correlation between the genotypes and phenotypes in PRPF31-related RP. Our findings expand the mutational spectrum of the PRPF31 gene and provide strong evidence that Alu elements of PRPF31 probably contribute to the susceptibility to genomic rearrangement in this locus.
视网膜色素变性（RP）是一种以视网膜不可逆性退变为特征的单基因疾病。PRPF31是常染色体显性RP的第二大常见致病基因，经常存在拷贝数变异（CNV），但其潜在机制尚不清楚。在本研究中，我们总结了18个携带PRPF31变异的RP家系（F01 - F18）的表型和基因型特征。在我们的中国RP家系队列中，PRPF31变异的发生率为1.7%（18/1024）。共检测到PRPF31的17种不同变异，其中包括8种新变异。值得注意的是，4种包含PRPF31的新CNV（占22.2%，4/18）经证实存在涉及同向Alu/Alu介导重排（AAMR）的大片段缺失。在总共12个断点定位到核苷酸分辨率的PRPF31的CNV中，10种变异（83.3%）可能由Alu元件介导。此外，我们描述了PRPF31相关RP的基因型与表型之间的相关性。我们的研究结果扩展了PRPF31基因的突变谱，并提供了有力证据表明PRPF31的Alu元件可能导致该位点基因组重排的易感性。
