Novel variants of RPGR in X-linked retinitis pigmentosa families and genotype-phenotype correlation
Novel variants of RPGR in X-linked retinitis pigmentosa families and genotype-phenotype correlation
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DOI：
10.5301/ejo.5000879
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发表时间：
2017-03-01
影响因子：
1.7
通讯作者：
Di Iorio, Enzo
中科院分区：
文献类型：
--
作者：
Parmeggiani, Francesco;Barbaro, Vanessa;Di Iorio, Enzo
目的：为了确定新的突变视网膜色素变性GT3调节（RPGR）基因和视网膜色素变性2（RP 2）基因潜在的X连锁视网膜色素变性（XLRP）和评估基因型-表型correlations.Methods：患者队列，由13个人从3个无关的XLRP家庭，进行了全面的眼科检查。用桑格测序法对每例患者的RPGR和RP 2开放阅读框进行分析。根据其病理效应，将所鉴定的遗传变异定义为突变或多态性。结果：共发现3种遗传变异：在RPGR基因外显子14上发现一个新的突变c.1591G>T，在外显子10上发现一个新的多态性c.1105C>T，分别导致RPGR基因的p.Glu531* 和p.Arg369Cys，在外显子2上发现一个已知的突变c.413A>G，从而导致RP 2基因的p.Glu138Gly。考虑到我们的XLRP先证者，RPGR相关的表型损伤与RP 2突变患者相似且较轻。另一方面，女性携带者的XLRP变异表现出不同的RPGR相关的后果，范围从杆功能减退c.1591G>T无义杂合性没有视网膜的变化c.1105C>T多态性heterozygosity.Conclusions：这些发现拓宽了频谱的RPGR突变和表型变异的疾病，这将是有用的遗传咨询和诊断在未来。
Purpose: To identify novel mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene and retinitis pigmentosa 2 (RP2) gene underlying X-linked retinitis pigmentosa (XLRP) and assess genotype-phenotype correlations.Methods: The patient cohort, consisting of 13 individuals from 3 unrelated XLRP families, underwent comprehensive ophthalmologic examination. The open reading frames of RPGR and RP2 were analyzed with Sanger sequencing in each patient. The identified genetic variants were defined as mutations or polymorphisms on the basis of their pathological effect.Results: We found 3 genetic variants: a novel mutation c.1591G>T in exon 14 and a novel polymorphism c.1105C>T in exon 10, resulting in p.Glu531* and p.Arg369Cys of RPGR gene, respectively, and one already known mutation c.413A>G in exon 2, resulting in a p.Glu138Gly of RP2 gene. Considering our XLRP probands, RPGR-related phenotypic damages were similar and less severe than those of the patient with the RP2 mutation. On the other hand, the female carriers of XLRP variants showed different RPGR-related consequences, ranging from rods hypofunctionality in c.1591G>T nonsense he terozygosity to no retinal changes in c.1105C>T polymorphic he terozygosity.Conclusions: These findings broaden the spectrum of RPGR mutations and phenotypic variability of the disease, which will be useful for genetic consultation and diagnosis in the future.