STUDIES OF HUMAN PIGMENTATION DISORDERS

描述(改编自《调查者摘要》)：因为他们 易见的临床表型，色素沉着障碍是在 第一个在人类中被发现的遗传病。其中最严重的是 眼皮肤白化病(OCA)综合征，其特征是显著减少 皮肤和眼睛的色素沉着，视力的主要发育缺陷 途径和随之而来的低视力，皮肤癌的易感性，以及 各种其他问题。一组特定的OCA障碍甚至更严重， 具有导致过早死亡的多效性全身症状。在这些 “多细胞器”型OCA，包括Hermansky-Pudlak综合征(HPS) 和切迪亚克综合征(CHS)，色素缺乏是由缺陷引起的 多种细胞器的生物发生，包括黑素小体、 色素的生物合成。我们之前已经确定了HPS和HPS的基因 CHS.在此，我们建议继续和扩展我们对卫生保健计划和社区卫生服务的研究， 重点研究HPS和CHS蛋白在植物体内的功能 细胞器发生和鉴定三个新的小鼠基因：light-ear， 可可和黄色，它们会导致小鼠的HPS样疾病，我们认为可能 同样会在人类中引起类似HPS的疾病。这些研究的意义将是 是为了阐明这些疾病的生物学基础，提供重要的 关于细胞器生物发生的基本知识，但更重要的是提供 可能导致开发特定和有效疗法的知识 预防HPS和CHS患者过早死亡。

DESCRIPTION (Adapted from the Investigator's Abstract): Because of their readily apparent clinical phenotypes, disorders of pigmentation were among the first genetic diseases recognized in humans. The most severe of these are the oculocutaneous albinism (OCA) syndromes, characterized by greatly reduced pigmentation of the skin and eyes, major developmental defects of the visual pathways and consequent low visual acuity, susceptibility to skin cancer, and various other problems. A specific group of OCA disorders is even more severe, with pleiotropic systemic manifestations that lead to premature death. In these "multi-organellar" forms of OCA, which include Hermansky-Pudlak syndrome (HPS) and Chediak-Syndrome (CHS), deficient pigmentation results from defective biogenesis of multiple cellular organelles, including the melanosome, the site of pigment biosynthesis. We have previously identified the genes for HPS and CHS. Here, we propose to continue and extend our studies of HPS and CHS, with particular emphasis on studying the functions of the HPS and CHS proteins in organellar biogenesis and identifying three novel mouse genes, light-ear, cocoa, and buff, which cause HPS-like disorders of the mouse and we believe may likewise cause HPS-like diseases in man. The significance of these studies will be to elucidate the biological basis of these disorders, providing important basic knowledge about organellar biogenesis, but more importantly providing knowledge that may lead to the development of specific and effective therapies to prevent the premature deaths of patients with HPS and CHS.