NEUROGLYCOPENIA--GENOTYPE/PHENOTYPE CORRELATION

描述：这项建议的目标是系统地研究 神经性低血糖患者队列以确定是否存在表型 葡萄糖GLUT-1基因特异性缺陷的相关性 被发现有5个点突变或无义突变的运输 或者到目前为止有17个病人。此外，Glut-1核型重排 在两名患者身上发现。这些发现表明，由此导致的突变 GLUT-1活性的丧失与表型的开始有关。这个 第一个目标是对现有患者进行基因分型 以及当新患者以大约 4/年。目标2的重点将是对 现有患者和新患者的表型。目标3将是开发Glut-1 通过同源重组缺陷小鼠，并进行 对这些动物进行神经病理学分析。

DESCRIPTION: The goal of this proposal are to systematically study a cohort of neuroglycopenia patients to determine if there is a phenotypic correlation with specific defects in the GLUT-1 gene, a glucose transported that has been found to have point or nonsense mutations in 5 or 17 patients so far. In addition, GLUT-1 karyotypic rearrangements have found in two patients. These findings indicate that mutations which result in a loss of GLUT-1 activity are linked to the onset of the phenotype. The first Aim will be carry out genotypic analysis on the existing patients and on new patients as they become available at a rate of approximately 4/year. The focus of Aim 2 will be an extensive characterization of the phenotype of existing and new patients. Aim 3 will be to develop GLUT-1 deficient mice by homologous recombination and to carry out a neuropathological analysis of these animals.