CHARACTERISTICS--GENES RESPONSIBLE FOR FAMILIAL HYPOPHOSPHATEMIC RICKETS

特征——导致家族性低磷酸盐性佝偻病的基因

• 批准号: 6220601
• 负责人: INGRID A HOLM
• 金额: $ 0.07万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6220601
• 关键词: gene mutation; genotype; human genetic material tag; inborn metabolism disorder diagnosis; linkage mapping; phenotype; phosphates; phosphorus metabolism; quantitative trait loci; vitamin D resistant rickets

The long-term objectives of this study are to characterize the gene defects leading to familial hypophosphatemic rickets (FHR), to understand how phosphate transport is regulated, and to lay the ground work for better therapy for affected individuals. PEX is the gene responsible for the most common form of FHR, X-linked hypophosphatemic rickets (HYP). In previous studies, no PEX mutation was detectable in about 50% of individuals with FHR, suggesting that some affected individuals may have autosomal dominant hypophosphatemic rickets (ADHR), another form of FHR for which the genetic defect is not known. The hypothesis is that mutations in genes other than PEX may lead to the HYP phenotype, and that these genes play an important role in phosphate transport. Specific Aims: 1) Analyze FHR patients for mutations in PEX 2) Perform a genotype-phenotype analysis of PEX mutations in patients with HYP 3) Identify a subset of patients with FHR and no detectable mutation in PEX, who will be used to search for other loci responsible for ADHR, with special emphasis on chromosomes 9 and 13

本研究的长期目标是描述导致家族性低磷血症佝偻病（FHR）的基因缺陷，了解磷酸盐运输是如何被调节的，并为更好地治疗受影响的个体奠定基础。PEX基因是导致最常见的FHR——x连锁低磷血症佝偻病（HYP）的基因。在先前的研究中，约50%的FHR患者未检测到PEX突变，这表明一些患者可能患有常染色体显性低磷血症佝偻病（ADHR），这是另一种形式的FHR，其遗传缺陷尚不清楚。假设PEX以外的基因突变可能导致HYP表型，并且这些基因在磷酸盐运输中起重要作用。具体目的：1)分析FHR患者的PEX突变2)对HYP患者的PEX突变进行基因型-表型分析3)确定FHR患者的一个亚群，PEX未检测到突变，将用于寻找与ADHR相关的其他基因座，特别强调9号和13号染色体