HUMAN BIOCHEMICAL GENETICS

人类生化遗传学

• 批准号: 3756625
• 负责人: W A GAHL
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3756625
• 关键词: Menkes' syndrome; child (0-11); clinical chemistry; cystinosis; enzyme activity; gene expression; gene mutation; genetic disorder; human genetic material tag; human subject; human tissue; inborn carbohydrate metabolism disorder; kidney disorder; linkage mapping; molecular genetics; oxygenases; tyrosinemias

1. Members of the Section continue to perform linkage analysis on several families with nephropathic cystinosis. To date, 75% of the human genome has been excluded as the location of the cystinosis gene. 2. Several mutations in the Menkes disease gene have been identified in patients with this X-linked disorder. Four members of a family with mild Menkes disease displayed an A to T transversion in the +3 splice donor site of an intron near the 3' end of the Menkes gene, resulting in deletion of a 118 bp exon, with substantial correct splicing. One patient with occipital horn syndrome had an A to G transition in the -2 exonic splice donor site in the middle of the Menkes gene resulting in deletion of a 92 bp exon, again with residual normal splicing. Two related patients with classical Menkes disease exhibited a G to T transversion at a -1 exonic splice donor site causing a glutamine to histidine substitution at codon 724, skipping of one, two, or three exons, and premature termination. 3. Analysis of N-linked oligosaccharides on serum glycoproteins from patients with Carbohydrate Deficient Glycoprotein Syndrome indicates a defect early in the formation of dolichol-oligosaccharides. 4. Mutational analysis of the fumarylacetoacetase gene in a 12-year old boy with chronic tyrosinemia type I revealed two defects, a missense mutation causing a tryptophan to glycine alteration in codon 234, and a splicing mutation in the +5 position of intron 12 causing exon skipping.

1。本节的成员继续对 几个患有肾脏病性囊肿的家庭。 迄今为止，人类的75％ 基因组被排除为囊肿基因的位置。 2。在Menkes疾病基因中的几个突变已在 患有这种X连锁疾病的患者。 一个家庭的四名成员 Menkes病在+3剪接供体中显示出A到T trans术 Menkes基因3'末端附近内含子的位置，导致 删除118 bp外显子，具有很大的正确剪接。 一 枕角综合征患者在-2中有A至G转变 在Menkes基因中间 删除92 bp外显子，再次带有剩余的正常剪接。 二 经典Menkes病的相关患者表现出A G至T 在-1个外部剪接供体部位的横向，导致谷氨酰胺 密码子724的组氨酸取代，跳过一，两个或三个 外显子和过早终止。 3。分析来自血清糖蛋白的N连接寡糖 碳水化合物缺乏糖蛋白综合征的患者表明 在形成多醇 - 寡糖的早期缺陷。 4。对12岁的富马乙酰乙酸乙酰乙酰基乙酸酶基因的突变分析 我患有慢性酪氨酸血症的男孩揭示了两个缺陷，一个错过 突变导致色氨酸在密码子234中的甘氨酸改变，A 内含子12的+5位置的剪接突变导致外显子跳过。