Carbohydrate Deficient Glycoprotein Syndromes

碳水化合物缺乏糖蛋白综合症

• 批准号: 6874834
• 负责人: Hudson H. Freeze
• 金额: $ 37.82万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6874834
• 关键词: Golgi apparatus; SDS polyacrylamide gel electrophoresis; carbohydrate biosynthesis; carbohydrate transport; clinical research; congenital disorders; electrospray ionization mass spectrometry; enzyme activity; gene mutation; glycoproteins; glycosphingolipids; glycosylation; glycosyltransferase; human subject; lectin; patient oriented research; polymerase chain reaction

DESCRIPTION (provided by applicant): Mutations in oligosaccharide biosynthesis cause Congenital Disorders of Glycosylation (CDG). This pathway requires scores of genes to insure proper glycosylation of proteins that cover the surface of every cell. Most of the 14 known types (causes) of CDG were discovered within the last 4 years. Many types of CDG await discovery. AIM 1 proposes to define the genes, mutations, and molecular basis of new types of CDG. CDG primarily affects the N-glycosylation pathway. We have now identified a group of CDG patients with defects in multiple glycosylation pathways. Among them are two siblings with mutations in a heterogeneous 8-member complex called COG (Conserved Oligomeric Golgi). COG organizes an efficient, glycosylation-competent Golgi. In AIM 2, we will knock down the cellular expression of each COG subunit to determine the effects on glycan biosynthesis and on the fate and functional localization of individual glycosyltransferases and nucleotide sugar transporters. This may help identify other similar COG-deficient patients and explain how COG deficiency compromises glycosylation. The common goal of these aims is to explain how these mutations cause glycosylation pathology. In the long run, we want to understand their physiological and molecular basis of new disorders and provide underpinnings for patient therapy.

描述（由申请人提供）：低聚糖生物合成突变导致先天性糖基化障碍（CDG）。这种途径需要大量的基因来确保覆盖每个细胞表面的蛋白质的适当糖基化。已知的14种CDG类型（病因）中的大多数是在最近4年内发现的。许多类型的CDG有待发现。AIM 1提出定义新型CDG的基因、突变和分子基础。