HUMAN FRUCTOSE-1,6-BISPHOSPHATASE GENE (FBP1) - EXON-INTRON ORGANIZATION, LOCALIZATION TO CHROMOSOME BANDS 9Q22.2-Q22.3, AND MUTATION SCREENING IN SUBJECTS WITH FRUCTOSE-1,6-BISPHOSPHATASE DEFICIENCY
HUMAN FRUCTOSE-1,6-BISPHOSPHATASE GENE (FBP1) - EXON-INTRON ORGANIZATION, LOCALIZATION TO CHROMOSOME BANDS 9Q22.2-Q22.3, AND MUTATION SCREENING IN SUBJECTS WITH FRUCTOSE-1,6-BISPHOSPHATASE DEFICIENCY
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DOI：
10.1006/geno.1995.1085
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发表时间：
1995-06-10
期刊：
影响因子：
4.4
通讯作者：
PILKIS, SJ
中科院分区：
文献类型：
--
作者：
ELMAGHRABI, MR;LANGE, AJ;PILKIS, SJ
1,6-二磷酸果糖酶 (EC 3.1.3.11) 是糖异生的关键调节酶，催化 1,6-二磷酸果糖水解生成 6-磷酸果糖和无机磷酸盐。由于糖异生受损，果糖 1,6-二磷酸酶缺乏与空腹低血糖和代谢性酸中毒有关。我们克隆并鉴定了人肝脏果糖-1,6-二磷酸酶基因（FBP1）。 FBP1通过荧光原位杂交定位于染色体带9q22.2-q22.3，由七个跨度>31 kb的外显子组成，六个内含子与大鼠基因中的位置相同。对两名果糖 1,6-二磷酸酶缺乏症受试者的 FBP1 突变进行了筛查。鉴定出四个核苷酸取代，其中两个是密码子中的沉默突变：Ala-216（条形下的 GC (T) --> 条形下的 GC (C) 和 Gly-319（条形下的 GG (G) --> 条形下的 GG (A)）。其他取代在内含子 3 中，在剪接供体位点下游 7 个核苷酸处有一个 C --> T 取代，在启动子区域，有一个 A --> T 取代 188 个核苷酸这些核苷酸取代也存在于正常未受影响的受试者中，因此不是所研究的两名受试者中果糖-1,6-双磷酸酶缺乏的原因。这些受试者中肝果糖-1,6-双磷酸酶缺乏的分子基础仍未确定，但可能是由于启动子中未识别的突变导致表达减少，或者是由于另一个基因的突变间接导致表达减少。果糖 1,6-二磷酸酶活性 (C) 1995 年学术出版社。
Fructose-1,6-bisphosphatase (EC 3.1.3.11) is a key regulatory enzyme of gluconeogenesis that catalyzes the hydrolysis of fructose-1,6-bisphosphate to generate fructose-6-phosphate and inorganic phosphate. Deficiency of fructose-1,6-bisphosphatase is associated with fasting hypoglycemia and metabolic acidosis because of impaired gluconeogenesis. We have cloned and characterized the human liver fructose-1,6-bisphosphatase gene (FBP1). FBP1, localized to chromosome bands 9q22.2-q22.3 by fluorescence in situ hybridization, consists of seven exons that span >31 kb, and the six introns are in the same position as in the rat gene. FBP1 was screened for mutations in two subjects with fructose-1,6-bisphosphatase deficiency. Four nucleotide substitutions were identified, two of which were silent mutations in the codons for Ala-216 (GC (T) under bar --> GC (C) under bar and Gly-319 (GG (G) under bar --> GG (A) under bar. The other substitutions were in intron 3, a C --> T substitution 7 nucleotides downstream from the splice donor site, and in the promoter region, an A --> T substitution 188 nucleotides upstream from the start of transcription. These nucleotide substitutions were also found in normal unaffected subjects and thus are not the cause of fructose-1,6-bisphosphatase deficiency in the two subjects studied. The molecular basis of hepatic fructose-1,6-bisphosphatase deficiency in these subjects remains undetermined but could result from unidentified mutations in the promoter that decrease expression or from mutations in another gene that indirectly lead to decreased fructose-1,6-bisphosphatase activity. (C) 1995 Academic Press, Inc.