HUMAN BIOCHEMICAL GENETICS

1.该科成员继续就以下问题进行联系分析 几个患有肾性胱氨酸病的家庭。迄今为止，75%的人类 基因组已被排除为胱氨酸病基因的位置。 2.在孟克斯病基因中发现了几个突变 患有这种X连锁障碍的患者。一个患有轻症的家庭的四人 在+3剪接供体中，Menkes病表现为A到T颠换 在Menkes基因3‘端附近的一个内含子的位置，导致 118个碱基对的外显子缺失，剪接基本正确。一 枕角综合征患者-2的A-G转换 位于Menkes基因中间的外显子剪接供体位点导致 92个碱基对的外显子缺失，同样带有残留的正常剪接。二 经典型门克斯病的相关患者表现为G到T A-1外显子剪接供体位置的颠换导致谷氨酰胺 密码子724处的组氨酸替换，跳过1、2或3 外显子和过早终止。 3.猪血清糖蛋白中N-寡糖的分析 碳水化合物缺乏性糖蛋白综合征患者提示 在二元醇-低聚糖形成的早期缺陷。 4.1例12岁儿童延胡索乙酸乙酯酶基因突变分析 患有慢性酪氨酸血症I型的男孩发现了两个缺陷，一个误解 导致密码子234中色氨酸到甘氨酸改变的突变，以及 内含子12+5位置的剪接突变导致外显子跳跃。

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.