Mutations in the promoter region of the aldolase B gene that cause hereditary fructose intolerance.
Mutations in the promoter region of the aldolase B gene that cause hereditary fructose intolerance.
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DOI：
10.1007/s10545-010-9192-5
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发表时间：
2010-12
影响因子：
4.2
通讯作者：
Tolan, Dean R.
中科院分区：
文献类型：
--
作者：
Coffee, Erin M.;Tolan, Dean R.
遗传性果糖不耐受症（HFI）是一种潜在的致命性遗传性代谢疾病，由肝脏和肾脏中的醛缩酶B活性缺乏引起。在ALDOB的蛋白质编码区中已知超过40种致病突变。ALDOB的蛋白质编码部分的上游突变在这里首次报道。61例HFI患者的DNA序列分析显示，启动子、内含子增强子和第一外显子中存在单碱基突变，这是完全未翻译的。一个突变，g.-132 G>A，位于启动子内转录因子结合位点内进化上保守的核苷酸处。第二个突变IVS 1 +1G>C位于第一个外显子的供体剪接位点。在体外电泳迁移率变动分析表明，在核提取物-蛋白结合在g.-132 G>A突变位点的减少。启动子突变导致使用荧光素酶报告质粒的转录降低。对来自用携带IVS 1 +1G>C突变的质粒转染的细胞的cDNA的分析导致异常剪接，从而导致第一内含子（~ 5 kb）的完全保留。IVS 1 +1G>C剪接突变导致报告质粒的荧光素酶活性丧失。ALDOB中的这些新突变代表美国HFI患者中2%的等位基因，其中IVS 1 +1G>C代表西班牙裔和非洲裔美国人种族的HFI患者中显著更高的等位基因频率（6%）。
Hereditary fructose intolerance (HFI) is a potentially fatal inherited metabolic disease caused by a deficiency of aldolase B activity in the liver and kidney. Over 40 disease-causing mutations are known in the protein-coding region of ALDOB. Mutations upstream of the protein-coding portion of ALDOB are reported here for the first time. DNA sequence analysis of 61 HFI patients revealed single base mutations in the promoter, intronic enhancer, and the first exon, which is entirely untranslated. One mutation, g.–132G>A, is located within the promoter at an evolutionarily conserved nucleotide within a transcription factor-binding site. A second mutation, IVS1+1G>C, is at the donor splice site of the first exon. In vitro electrophoretic mobility shift assays show a decrease in nuclear extract-protein binding at the g.–132G>A mutant site. The promoter mutation results in decreased transcription using luciferase reporter plasmids. Analysis of cDNA from cells transfected with plasmids harboring the IVS1+1G>C mutation results in aberrant splicing leading to complete retention of the first intron (~ 5 kb). The IVS1+1G>C splicing mutation results in loss of luciferase activity from a reporter plasmid. These novel mutations in ALDOB represent 2% of alleles in American HFI patients, with IVS1+1G>C representing a significantly higher allele frequency (6%) among HFI patients of Hispanic and African-American ethnicity.
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DOI：
10.1006/bbrc.1995.1128
发表时间：
1995-01-26
影响因子：
3.1
作者：
DOYLE, SA;TOLAN, DR
通讯作者：
TOLAN, DR
影响因子：
4
作者：
James, CL;Rellos, P;Cox, TM
通讯作者：
Cox, TM
DOI：
10.1016/s0006-291x(05)80244-x
发表时间：
1991-04-30
影响因子：
3.1
作者：
GREGORI, C;GINOT, F;PICHARD, AL
通讯作者：
PICHARD, AL
影响因子：
--
作者：
Park HD;Kim YK;Park KU;Kim JQ;Song YH;Song J
通讯作者：
Song J
影响因子：
5.9
作者：
LAMEIRE, N;MUSSCHE, M;RINGOIR, S
通讯作者：
RINGOIR, S