Edwards A O, Klein M L, Berselli C B, Hejtmancik J F, Rust K, Wirtz M K, Weleber R G, Acott T S
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, USA.
Am J Ophthalmol. 1998 Sep;126(3):417-24. doi: 10.1016/s0002-9394(98)00097-x.
To study the phenotypic variability in patients inheriting the disease gene for malattia leventinese (dominant macular drusen) and refine the localization of the gene.
A family with dominant radial drusen was ascertained and studied with clinical examination and DNA linkage analysis. Inheritance of the disease gene was determined by DNA analysis and used to document the variability in phenotypic expression.
Fifty family members were studied with fundus photography and genotyping. Linkage analysis showed that the disease in this family was linked to chromosome 2p16-21 with a maximum lod score of 3.72 at D2S2153. An affected patient with obligate recombinations allowed refinement of the disease interval to a 6.2-cM region between D2S2227 and D2S378. The phenotype of older affected patients varied from severe geographic atrophy or subretinal fibrosis to a single druse adjacent to the optic disk. Small and medium-sized, nonradial, and soft macular drusen seen in four older individuals in the family were not specifically associated with the disease haplotype.
Refinement of the localization of the gene for malattia leventinese will facilitate its positional cloning. Genotypic documentation of the variable expression of the disease shows that a single, large, subretinal druse adjacent to the optic disk is consistent with inheritance of the disease gene. Soft macular drusen in low abundance were not specifically associated with inheritance of the disease gene. These results will facilitate the genetic counseling of patients with malattia leventinese. It is unknown what proportion of age-related macular degeneration arises from mutations in disease genes for dominant drusen.
研究遗传性莱文廷斯病（显性黄斑玻璃疣）患者的表型变异性，并优化该疾病基因的定位。
确定一个患有显性放射状玻璃疣的家系，并通过临床检查和DNA连锁分析进行研究。通过DNA分析确定疾病基因的遗传情况，并用于记录表型表达的变异性。
对50名家庭成员进行了眼底照相和基因分型。连锁分析表明，该家系中的疾病与2号染色体p16 - 21区域连锁，在D2S2153处的最大对数优势得分为3.72。一名有明确重组的患病患者使得疾病区间缩小至D2S2227和D2S378之间6.2厘摩的区域。老年患病患者的表型从严重的地图状萎缩或视网膜下纤维化到视盘旁单个玻璃疣不等。在该家系中4名老年人中发现的中小尺寸、非放射状和软性黄斑玻璃疣与疾病单倍型无特异性关联。
莱文廷斯病基因定位的优化将有助于其定位克隆。该疾病可变表达的基因分型记录表明，视盘旁单个大的视网膜下玻璃疣与疾病基因的遗传一致。低丰度的软性黄斑玻璃疣与疾病基因的遗传无特异性关联。这些结果将有助于莱文廷斯病患者的遗传咨询。尚不清楚年龄相关性黄斑变性中有多大比例是由显性玻璃疣疾病基因的突变引起的。
