GENETIC LINKAGE STUDY MACULAR CORNEAL DYSTROPHY

黄斑角膜营养不良（MCD）是一种罕见的常染色体隐性遗传性眼病， 导致进行性双侧视力丧失的胆积病。 临床 疾病的进展通常会导致视力障碍， 第二个十年的生活，一般直到穿透性角膜移植术 （角膜移植）通常需要通过 人生的第四个十年 硫酸角质素样糖胺聚糖 积聚在角膜中。 MCD基因的位置尚不清楚， 没有症状前诊断测试可用于个人谁是在 风险 也没有一种可靠的载体检测形式。 这项研究的目的是确定 MCD基因，同时尝试表征存储 实质内容。 参与者将从受影响的登记册中选出。 由委托人抚养的个人及其未受影响的亲属 调查员 将从受影响的个体中采集血样， 他们的父母和兄弟姐妹建立淋巴母细胞系， DNA的永久来源。 此外，将对血清进行特定 已知硫酸角质素的表位显著降低 在许多受影响的人。 限制性MCD连锁分析 片段长度多态性随机分布在整个基因组中， 以及候选基因，成为可用的将进行使用 最先进的统计方法 建立联系关系和确定 染色体定位是鉴定基因的第一步。 罚款 基因定位、基因表达、异常积累的性质，以及 那么它的产生机制就可能成为可能。 此外 建立联系关系可以澄清 这种疾病的遗传异质性 这些发展将导致一个 MCD的症状前诊断方法和MCD携带者的检测 MCD基因。 最终这项工作可能会导致一种替代的治疗方法 当进一步的基因工程技术变得可用时。

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.