Molecular characterization of a case of atransferrinemia
Molecular characterization of a case of atransferrinemia
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DOI：
10.1182/blood.v96.13.4071.h8004071_4071_4074
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发表时间：
2000-12-15
期刊：
影响因子：
20.3
通讯作者：
Fairbanks, VF
中科院分区：
文献类型：
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作者：
Beutler, E;Gelbart, T;Fairbanks, VF
遗传性无转铁蛋白血症是一种罕见但有指导意义的疾病，以前仅在6个家庭的8例患者中报道。其特征在于小红细胞性贫血和铁负荷，并可通过血浆输注有效治疗。我们现在报告在美国已知的第一例。我们确定了人类转铁蛋白基因外显子的侧翼序列，并对患者及其父母的DNA的所有外显子和一些侧翼区域进行了测序。患者的DNA显示了10个碱基对（bp）的缺失，随后是9个碱基对的重复序列插入。在互补DNA（cDNA）nt 1429处也存在G->C颠换，预示着氨基酸位置477（Ala 477 Pro）处的丙氨酸被脯氨酸取代。后一种突变发生在进化上高度保守的位点;筛选了704个对照等位基因，没有发现这种点突变。患者的每个转铁蛋白基因都含有一个突变，即患者是这些突变的复合杂合子，因为在她的父母中都发现了一个突变。除了这些突变，我们认为这是病人的无转铁蛋白血症的原因，在外显子13的cDNA 1572 G-->C沉默多态性，以及2个以前未报道的多态性IVS 8 + 62 c-->t和IVS 14 -4 c-->a。普通人群中nt 1572和intron 8突变较为常见，intron 14突变较少见。(C)2000年，美国血液学会。
Hereditary atransferrinemia is a rare but instructive disorder that has previously been reported in only 8 patients in 6 families. It is characterized by microcytic anemia and by iron loading, and can be treated effectively by plasma infusions. We now report the first case known in the United States. We determined the sequences flanking the exons of the human transferrin gene and sequenced all of the exons and some of the flanking regions of the patient's DNA and that of her parents. The patient's DNA revealed a 10-base pair (bp) deletion, followed by a 9-bp insertion of a duplicated sequence. There was also a G-->C transversion at complementary DNA (cDNA) nt 1429, predicting that a proline was substituted for the alanine in amino acid position 477 (Ala 477 Pro). The latter mutation occurs at an evolutionarily highly conserved site; 704 control alleles were screened and this point mutation was not found. Each of the patient's transferrin genes contains one mutation, ie, the patient is a compound heterozygote for these mutations, because one was found in each of her parents. In addition to these mutations, which we regard to be causative in the patient's atransferrinemia, a silent polymorphism at cDNA 1572 G-->C was found in exon 13 as well as 2 previously unreported polymorphisms at IVS8 + 62 c-->t and IVS14-4 c-->a. The mutation in nt 1572 and that in intron 8 were common in the general population; the intron 14 mutation is rare. (C) 2000 by The American Society of Hematology.