Novel PRPF31 and PRPH2 Mutations and Co-occurrence of PRPF31 and RHO Mutations in Chinese Patients With Retinitis Pigmentosa
Novel PRPF31 and PRPH2 Mutations and Co-occurrence of PRPF31 and RHO Mutations in Chinese Patients With Retinitis Pigmentosa
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DOI：
10.1001/archophthalmol.2009.112
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发表时间：
2009-06-01
影响因子：
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通讯作者：
To, Chi Ho
中科院分区：
文献类型：
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作者：
Lim, King Poo;Yip, Shea Ping;To, Chi Ho
目的：筛选中国视网膜色素变性（RP）患者PRPF31、RHO和PRPH2基因的突变。方法：从香港视网膜学会招募RP患者。对PRPF31、RHO和PRPH2基因的所有外显子进行扩增，并利用单链构象多态性分析和DNA测序进行突变筛选。在患者和对照组中测定序列改变的频率。结果：54个家族的76例患者中，鉴定出3个致病突变和32个非致病序列改变。一个常染色体显性RP家族被发现含有一种新的截断PRPF31突变（p. Phe262SerfsX59）和一种已知的错义RHO突变（p. Pro347Leu）， 1名受影响的妇女对这两种突变都是杂合的。一个单纯性RP病例是由一种新的截断PRPH2突变（p. Ala78LeufsX99）引起的。32个非致病性序列变化中有13个是新的，在RP患者和对照组中发现的频率很低。结论：PRPF31、RHO和PRPH2突变在中国RP患者中出现频率较低（9个常染色体显性RP家族中有1个），PRPF31和PRPH2截断突变是新发现的。临床相关性：需要在中国患者中寻找RP的共同病因。两种不同基因突变的共同出现可能改变表型的严重程度。临床相关性：需要在中国患者中寻找RP的共同病因。两种不同基因突变的共同出现可能改变表型的严重程度。
Objective: To screen mutations in the PRPF31, RHO, and PRPH2 genes in Chinese patients with retinitis pigmentosa (RP).Methods: Patients with RP were recruited from Retina Hong Kong. All the exons of the PRPF31, RHO, and PRPH2 genes were amplified and screened for mutations using single-stranded conformation polymorphism analysis followed by DNA sequencing. Frequencies of sequence changes were determined in patients and controls.Results: In 76 patients from 54 families, 3 pathogenic mutations and 32 nonpathogenic sequence changes were identified. One family with autosomal dominant RP was found to harbor a novel truncating PRPF31 mutation (p. Phe262SerfsX59) and a known missense RHO mutation (p. Pro347Leu), and 1 affected woman was heterozygous for both mutations. One simplex RP case was caused by a novel truncating PRPH2 mutation (p. Ala78LeufsX99). Thirteen of the 32 nonpathogenic sequence changes were novel and were found in low frequencies in patients with RP and controls.Conclusions: Mutations in PRPF31, RHO, and PRPH2 were found in low frequencies (1 of 9 autosomal dominant RP families) in Chinese patients, and the PRPF31 and PRPH2 truncating mutations were novel. Clinical Relevance: A search for a common cause for RP in Chinese patients is needed. The co-occurrence of 2 different gene mutations may modify the phenotype severity.Clinical Relevance: A search for a common cause for RP in Chinese patients is needed. The co-occurrence of 2 different gene mutations may modify the phenotype severity.