El Matri Leila, Ambresin Aude, Schorderet Daniel F, Kawasaki Aki, Seeliger Mathias W, Wenzel Andreas, Arsenijevic Yvan, Borruat François-Xavier, Munier Francis L
Hedi Rais Institute of Ophthalmology, Tunis, Tunisia.
Graefes Arch Clin Exp Ophthalmol. 2006 Sep;244(9):1104-12. doi: 10.1007/s00417-005-0096-2. Epub 2006 Feb 28.
To identify the genetic defect, and to phenotype, three consanguineous Tunisian families presenting with early-onset retinal degeneration (EORD).
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.
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.
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.
确定三个患有早发性视网膜变性（EORD）的突尼斯近亲家庭的基因缺陷并进行表型分析。
纳入所有可及的家庭成员。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视网膜电图（ERG）和瞳孔测量。启动了全基因组连锁分析。通过双向测序对连锁区间内的RPE65基因进行突变分析。
在53名接受检查的成员中，有11名临床上患有EORD。连锁分析显示，位于1p31的标记D1S207的最大对数优势得分为4.02（θ=0.1）。RPE65基因的突变筛查在所有受影响个体中鉴定出一个与疾病共分离的纯合R91W突变。11名纯合子有眼球震颤，视力从眼前指数（CF）到无光感（NLP）不等。识别出两种视网膜模式：模式1表现为中周部深层白色点状沉积物，几乎没有色素沉着团块；而模式2显示中周部色素沉着团块，没有任何白色沉积物。纯合子未检测到全视野ERG，瞳孔对光反射异常。11名杂合子视觉功能正常。
我们在突尼斯东北部的一个近亲人群中鉴定并表征了一种早发性视锥视杆营养不良的地方病形式，这是由于单一RPE65突变的流行所致。识别出两种眼底模式：早期为白色点状沉积物，后期为色素沉着团块。
