HEREDITARY MACULAR DEGENERATION

遗传性黄斑变性包括大量的不良 一组容易理解和混淆的疾病， 中央视觉 有些黄斑病变有典型的孟德尔式 遗传模式和个别罕见，而其他 黄斑病变，如年龄相关性黄斑病变（ARM），显然是 遗传影响（但非孟德尔遗传），并非常 因此，这是一个重大的公共卫生难题。 正是这些少 常见的黄斑病变与经典的遗传模式，这是更多 适用于强大的分子遗传学方法，更有可能 揭开黄斑功能和功能障碍的基本奥秘。 的 从这些罕见的疾病中获得的理解和知识， 适用于更常见的疾病，如年龄相关性黄斑病变。 总体方法将是充分表征一个黄斑特异性 疾病，表示为MCDR 1，临床上，电生理学， 从精神病理学和分子学的角度来研究这种基因在ARM中的作用 以及其他黄斑病变。 MCDR患者1 表型与ARM有许多相似之处，除了早期的 发病年龄 由于这些相似之处， MCDR1将揭示ARM和黄斑特异性功能的见解。的PI 最近阐明了临床认识，分类和基因 MCDR1的定位。 下一步将是确定突变 导致MCDR 1，这将涉及使用几种新技术 如染色体显微切割、新基因富集克隆 标记和选择性杂交克隆。 然后从基因型到表现型 将进行相关性。MCDR1基因将被用作候选基因 对于其他遗传影响的黄斑疾病，如ARM，锥 黄斑缺损变性和类似的不治之症。

The hereditary macular degenerations encompass a large number of poorly understood and confusing group of diseases which cause impairment of central vision. Some of these maculopathies have a classical Mendelian inheritance pattern and are individually uncommon while other maculopathies, such as age-related maculopathy (ARM), apparently are genetically influenced (but with non-Mendelian inheritance) and are very common thus representing a major public health dilemma. It is these less common maculopathies with classical inheritance patterns which are more amenable to powerful molecular genetic approaches and more likely to unlock the basic mysteries of macular function and dysfunction. The understanding and knowledge gained from these rarer disorders, can then be applied to more common diseases such as age-related maculopathy. The overall approach will be to fully characterize one macular specific disease, denoted MCDR1, clinically, electrophysiologically, psychophysically and molecularly and investigate this gene's role in ARM as well as other maculopathies. Patients affected with the MCDR1 phenotype have many similarities to ARM with the exception of the earlier age of onset. Because of these similarities, the full characterization of MCDR1 will reveal insights into ARM and macular specific function. The PI has recently clarified the clinical understanding, classification and gene localization of MCDR1. The next step will be to identify the mutation causing MCDR1, this will involve using in concert several new techniques such as chromosomal micro-dissection, enrichment cloning of new genetic markers and selective hybridization cloning. Then a genotype to phenotype correlation will be made. The MCDR1 gene will be used as a candidate gene for other genetically influenced macular disorders such as ARM, cone degeneration macular colobomata and similar incurable diseases.