Phenotype of three consanguineous Tunisian families with early-onset retinal degeneration caused by an R91W homozygous mutation in the RPE65 gene
Phenotype of three consanguineous Tunisian families with early-onset retinal degeneration caused by an R91W homozygous mutation in the RPE65 gene
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DOI：
10.1007/s00417-005-0096-2
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发表时间：
2006-09-01
影响因子：
2.7
通讯作者：
Munier, Francis L.
中科院分区：
文献类型：
--
作者：
El Matri, Leila;Ambresin, Aude;Munier, Francis L.
目的：确定遗传缺陷，并对表型，三个近亲突尼斯家庭呈现早发性视网膜变性（EORD）。方法：纳入所有可接近的家庭成员。他们接受了血液采样和眼科检查，包括在可能的情况下进行全视野电图和瞳孔测量。启动了全基因组连锁分析。通过双向测序对RPE65基因在连锁区间内的突变进行分析。结果：53名被检查的成员中有11人临床患有EORD。连锁分析显示，1p31上的标记D1S207的最大负载评分为4.02 （theta=0.1）。RPE65基因的突变筛选在所有受影响的个体中发现了与疾病共分离的纯合子R91W突变。11个纯合子有眼震和视力，范围从CF到NLP。我们发现了两种视网膜模式：模式1呈现外周中部深白点沉积，几乎没有团块性色素沉着，而模式2显示外周中部色素沉着，没有任何白色沉积。纯合子没有可检测到的全视野ERG和异常的瞳孔光反射。11个杂合子视力正常。结论：由于单一RPE65突变的流行，我们在突尼斯东北部的一个近亲人群中发现并描述了一种地方性的早发性杆状锥体营养不良。两种眼底镜模式确定：白点沉积在早期阶段和结块色素在后期阶段。
Purpose: To identify the genetic defect, and to phenotype, three consanguineous Tunisian families presenting with early-onset retinal degeneration (EORD).Methods: All accessible family members were included. They underwent blood sampling and ophthalmological examination including, when possible, full-field ERG and pupillometry. A genome-wide linkage analysis was initiated. Mutation analysis of the RPE65 gene within the linked interval was performed by bi-directional sequencing.Results: Eleven out of 53 examined members were clinically affected with an EORD. Linkage analysis revealed a maximal lod score of 4.02 (theta=0.1) for the marker D1S207 on 1p31. Mutational screening of the RPE65 gene identified a homozygous R91W mutation co-segregating with the disease in all affected individuals. Eleven homozygotes had nystagmus and acuities ranging from CF to NLP. Two retinal patterns were identified: pattern 1 presented mid-peripheral deep white dot deposits and virtually no clumped pigmentation, whereas pattern 2 showed mid-peripheral pigmented clumps without any white deposits. Homozygotes had no detectable full-field ERG and an abnormal pupillary light reflex. Eleven heterozygotes had normal visual function.Conclusion: We identified and characterised an endemic form of early onset rod-cone dystrophy in a consanguineous population from northeastern Tunisia, due to the prevalence of a single RPE65 mutation. Two funduscopic patterns were identified: white dot deposits in earlier stages and clumped pigment in later stages.