GENETIC LINKAGE STUDY MACULAR CORNEAL DYSTROPHY

黄斑性角膜营养不良是一种罕见的常染色体隐性遗传性眼病。 导致进行性双眼视力丧失的贮积性疾病。临床 疾病的发展通常会导致视力障碍 生命第二个十年，通常恶化到穿透性角膜移植 (角膜移植)需要恢复视力，通常由 生命的第四个十年。一种类似于糖胺聚糖的硫酸角蛋白 积聚在角膜中。MCD的基因位置未知， 无症状前诊断测试可用于以下个人： 风险。也没有一种可靠的载波检测形式。 这项拟议的研究的目标是确定人类基因组的位置 MCD基因(S)同时试图描述储藏特性 实质性的。参与者将从受影响的注册表中选出 由委托人供养的个人及其未受影响的亲属 调查员。血液样本将从受影响的个人身上获取， 他们的父母和兄弟姐妹建立淋巴母细胞系作为 DNA的永久来源。此外，血清将被检测出一种特定的 已知被显着还原的硫酸角蛋白硫酸盐的表位 在许多受影响的个体中。MCD带约束的连锁性分析 在基因组中随机分布的片段长度多态 以及变得可用的候选基因将使用 最先进的统计方法。 一种连锁关系的建立和鉴定 染色体定位是鉴定基因的第一步。很好 基因图谱，基因表达，异常堆积的性质，以及 到那时，它的生成机制可能成为可能。此外 建立联系关系可以澄清以下可能性 这种疾病的遗传异质性。这些发展将导致 MCD的症状前诊断及携带者的检测方法 MCD基因。最终，这项工作可能会带来另一种治疗方法 当进一步的基因工程技术变得可用时，MCD。

Macular corneal dystrophy (MCD) is a rare, autosomal recessive ocular storage disease which leads to progressive bilateral visual loss. Clinical progression of the disease usually causes visual impairment during the second decade of life and generally worsens until penetrating keratoplasty (cornea transplantation) is required to restore vision usually by the fourth decade of life. A keratan sulfate like glycosaminoglycan accumulates in the cornea. The location of the gene for MCD is unknown and no presymptomatic diagnostic test is available to individuals who are at risk. Nor is there a reliable form of carrier detection. The objective of the proposed research is to define the genomic location of the MCD gene(s) while concurrently attempting to characterize the storage substance. Participants will be selected from a registry of affected individuals and their unaffected relatives maintained by the Principal Investigator. Blood samples will be obtained from affected individuals, their parents, and siblings to establish lymphoblastoid cell lines as permanent sources of DNA. In addition, serum will be tested for a specific epitope of sulfated keratan sulfate which is known to be markedly reduced in many affected individuals. Linkage analysis of MCD with restriction fragment length polymorphisms randomly located throughout the genome as well as candidate genes that become available will be performed using state-of-the-art statistical methodology. The establishment of a linkage relationship and identification of the chromosomal location are the first steps in identifying the gene. Fine gene mapping, gene expression, the nature of the abnormal accumulates, and its mechanism of generation may then be possible. In addition establishment of linkage relationships may clarify the possibility of genetic heterogeneity in this disorder. These developments will lead to a method of presymptomatic diagnosis of MCD and detection of carriers of the MCD gene. Eventually the work may lead to an alternative means of treating MCD when further techniques of genetic engineering become available.