GENETIC-LINKAGE OF WAGNER DISEASE AND EROSIVE VITREORETINOPATHY TO CHROMOSOME 5Q13-14
GENETIC-LINKAGE OF WAGNER DISEASE AND EROSIVE VITREORETINOPATHY TO CHROMOSOME 5Q13-14
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DOI：
10.1001/archopht.1995.01100050139045
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发表时间：
1995-05-01
影响因子：
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通讯作者：
STONE, EM
中科院分区：
文献类型：
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作者：
BROWN, DM;GRAEMIGER, RA;STONE, EM
背景：瓦格纳病和糜烂性玻璃体视网膜病变是潜在致盲的常染色体显性遗传疾病，与 Stickler 综合征有一些相似之处。然而，这两种疾病都伴有视网膜色素上皮变化、夜视能力差、视野缺损和视网膜电图异常，而这些在 COL2A1 相关 Stickler 综合征家族中并未发现。此外，孔源性视网膜脱离在瓦格纳病中并不常见，但在大约 50% 的 Stickler 综合征或糜烂性玻璃体视网膜病变患者中发生。 目的： 确定与瓦格纳病和糜烂性玻璃体视网膜病变相关的基因的染色体位置，并从遗传上区分这些疾病与 Stickler 综合征。 方法： 患有糜烂性玻璃体视网膜病变的家庭中 15 名受影响的成员玻璃体视网膜病变和 Wagner 描述的家系的 24 个受影响的后代通过分布在基因组中的一组短串联重复多态性进行了基因分型。结果：在每个家族中观察到疾病表型和映射到染色体 5q13-14 的标记之间存在显着关联。患有糜烂性玻璃体视网膜病变的家庭的最高 Lod 评分为 4.2，通过标记 GATA3H06 (theta=0) 获得。瓦格纳病家族的最高 lod 得分为 5.8，通过标记 D5S815 (theta=0) 获得。对已知位于连锁间隔附近的候选基因（软骨连接蛋白）进行了突变筛查，但在两个家族中均未发现突变。结论：这些数据表明糜烂性玻璃体视网膜病变和瓦格纳病是等位基因疾病，并证明它们在遗传上与 COL2A1 相关的 Stickler 综合征不同。
Background: Wagner disease and erosive vitreoretinopathy are potentially blinding autosomal dominant diseases that share some similarities with Stickler syndrome. However, both disorders have associated retinal pigment epithelial changes, poor night vision, visual field defects, and abnormal electroretinographic findings, which are not found in families with COL2A1-associated Stickler syndrome. In addition, rhegmatogenous retinal detachments are uncommon in Wagner disease but occur in approximately 50% of patients with either Stickler syndrome or erosive vitreoretinopathy.Objectives: To identify the chromosomal location of the genes involved in Wagner disease and erosive vitreoretinopathy and to distinguish these conditions genetically from Stickler syndrome.Methods: Fifteen affected members of a family affected with erosive vitreoretinopathy and 24 affected descendants of the pedigree described by Wagner were genotyped with a set of short tandem repeat polymorphisms distributed across the genome.Results: Significant linkage was observed in each family between the disease phenotype and markers that map to chromosome 5q13-14. The highest lod score for the family affected with erosive vitreoretinopathy was 4.2 and was obtained with marker GATA3H06 (theta=0). The highest lod score for the family affected with Wagner disease was 5.8 and was obtained with marker D5S815 (theta=0). A candidate gene (cartilage link protein) that is known to lie near the linked interval was screened for mutations, but none was found in either family.Conclusions: These data suggest that erosive vitreoretinopathy and Wagner disease are allelic disorders and demonstrate that they are genetically distinct from COL2A1-associated Stickler syndrome.