Rhodopsin p.N78I dominant mutation causing sectorial retinitis pigmentosa in a pedigree with intrafamilial clinical heterogeneity
Rhodopsin p.N78I dominant mutation causing sectorial retinitis pigmentosa in a pedigree with intrafamilial clinical heterogeneity
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DOI：
10.1016/j.gene.2013.01.048
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发表时间：
2013-04-25
期刊：
影响因子：
3.5
通讯作者：
Carlos Zenteno, Juan
中科院分区：
文献类型：
--
作者：
Rivera-De la Parra, David;Cabral-Macias, Jesus;Carlos Zenteno, Juan
目的：本研究的目的是确定色素性视网膜炎（RP）的分子基础在4个受影响的兄弟姐妹家族分离视网膜表型。方法：受影响的兄弟姐妹进行了全面的眼科检查，包括眼底检查、视网膜电图、荧光素血管造影、视野测量和光学相干断层扫描。父母都在60多岁后去世，据报道没有视力障碍。分子分析包括在4个患病同胞的DNA中对染色体3q21-q24处的视紫红质基因（RHO）进行直接核苷酸测序。共有200个种族匹配的等位基因作为突变对照。结果：该家族有临床记录的RP区。观察到广泛的表型变异，视力范围为20/20至20/200，眼底镜外观变化。分子分析显示，在RHO外显子1上存在c.233A>T突变，预测p.N78I的错义替换。结论：尽管RP可由多种基因突变引起，但选择RHO基因在该RP家族中进行研究，因为它先前与扇形疾病有关。本病例体现了基于眼底特征指导RP分子分析的价值。(C) 2013 Elsevier B.V.版权所有
Objective: The purpose of this study was to determine the molecular basis of retinitis pigmentosa (RP) in a 4 affected sib-family segregating this retinal phenotype.Methods: Affected sibs underwent complete ophthalmologic examination including funduscopic inspection, electroretinogram, fluorescein angiography, visual field measurement, and optical coherence tomography. Both parents were deceased after their sixties and were reported with no visual handicap. Molecular analysis included direct nucleotide sequencing of the rhodopsin gene (RHO), at chromosome 3q21-q24, in DNA from a total of 4 affected sibs. A total of 200 ethnically matched alleles were included as mutation controls.Results: Sector RP was clinically documented in this family. Wide phenotypic variability was observed with visual acuities ranging from 20/20 to 20/200 and variable funduscopic appearance. Molecular analysis disclosed a c.233A>T mutation at RHO exon 1, predicting a missense p.N78I substitution.Conclusions: Even though RP can be caused by mutations in a variety of genes, the RHO gene was chosen to be investigated in this RP family since it has been previously associated to sector disease. This case exemplifies the value of guiding RP molecular analysis based on funduscopic features. (C) 2013 Elsevier B.V. All rights reserved.