GENETIC CHARACTERIZATION OF ALPORT SYNDROME

阿尔波特综合征的遗传特征

• 批准号: 3239216
• 负责人: CURTIS L ATKIN
• 金额: $ 17.04万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-03-01 至 1992-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3239216
• 关键词: DNA; Goodpasture's syndrome; autosomal dominant trait; biopsy; chromosome deletion; congenital deafness; gel electrophoresis; genetic counseling; genetic disorder; genetic disorder diagnosis; genetic mapping; genetic markers; genetic transcription; genotype; glomerulonephritis; human population genetics; kidney transplantation; linkage mapping; major histocompatibility complex; molecular pathology; nephritis; nucleic acid probes; nucleic acid sequence; sex chromosomes; skin

Alport syndrome (AS) denominates a heterogeneous group of hereditary chronic progressive glomerulonephritides that are characterized by similar nephrologic symptoms and by similar progressive degeneration of glomerular capillary epithelial basement membranes (GBM). The etiology of AS is unknown but is thought to involve defects of GBM structural proteins. Disease frequency is greater than or equal to 1 in 5,000. Most affected males experience end-stage renal disease (ESRD), and they account for 2-4% of males that receive dialysis or kidney transplantation. Phenotypic heterogeneity of AS among different kindreds includes eye defects, thrombocytopathia, and/or progressive sensorineural deafness, and rate of progression of renal failure. Genotypic heterogeneity is reported to include autosomal as well as the more clearly established X-linked inheritance. The long-term objective of this application is to determine the genetic and biochemical bases of AS in order that specific and effective treatments or prevention might be developed. We propose to better define the phenotypes, and to use linkage of nephritis to X-linked restriction fragment length polymorphic markers (RFLPs) to precisely map the chromosomal locus for each of three X-linked AS phenotypes found among 23 Utah kindreds. We have already shown that two types of AS among the three largest Utah kindreds are loosely linked to DNA probes in the middle of the long arm of the X chromosome. We propose to construct a high-resolution genetic linkage map of this region of the X with currently available probes and ones we plan to develop. By mapping the AS gene(s) within this genetically well-defined region, we expect to test the hypothesis of genetic heterogeneity for X-linked AS, to improve the process of genetic diagnosis and counseling for this disease, and to develop an approach to the identification and cloning of the defective gene(s). We also propose to determine whether X-chromosome deletions cause AS: the existence of deletions would improve the prospects for rapid identification of the normal gene(s) that are missing in AS.

阿尔波特综合征（AS）是一种异质的类群