Dominant thalassemia-like phenotypes associated with mutations in exon 3 of the beta-globin gene.
Dominant thalassemia-like phenotypes associated with mutations in exon 3 of the beta-globin gene.
复制标题
与 β-珠蛋白基因外显子 3 突变相关的显性地中海贫血样表型。
作者：
H. Kazazian;C. Dowling;Richard Hurwitz;M. Coleman;Alison Stopeck;J. Adams
在疟疾流行地区，产生β-地中海贫血的突变达到大于0.01的个体基因频率，因为β-地中海贫血性状个体的遗传适应性比正常个体高。β-珠蛋白基因的外显子3作为常见的β-地中海贫血突变位点相对较少。由单核苷酸丢失和无义突变引起的移码，当它们发生在外显子1和2时，产生β-地中海贫血性状。相反，当存在于外显子3时，它们通常产生慢性溶血性贫血。外显子3中的某些错义突变产生不稳定的球蛋白和杂合子中伴有溶血的中间型地中海贫血。在这里，我们报告两个新的突变外显子3的β-珠蛋白基因。一个是在密码子109的单核苷酸缺失在一个78岁的立陶宛人慢性溶血性贫血和地中海贫血的特点。它导致一种异常的珠蛋白（β曼哈顿），被延长到156个氨基酸。第二个是密码子127处的CAG-CGG错义突变，其导致Gln-Pro取代（β Houston）和中间型地中海贫血伴溶血，发生在一个英裔美国家庭的三代人中。虽然这两个患者的临床表型差异不大，珠蛋白合成比率的差异是显着的，大概反映了每个异常β-珠蛋白形成α-β二聚体的能力的差异。高频外显子3突变的缺乏及其在世界范围内的分布可能归因于其表型严重性和相对维斯疟疾的遗传适应性增加的损失。
Mutations producing beta-thalassemia reach individual gene frequencies greater than .01 in malarial-endemic regions because beta-thalassemia trait individuals have increased genetic fitness over that of normal individuals. Exon 3 of the beta-globin gene has been relatively spared as a site of common beta-thalassemia mutations. Frameshifts caused by the loss of a single nucleotide and nonsense mutations produce beta-thalassemia trait when they occur in exons 1 and 2. In contrast, they usually produce chronic hemolytic anemia when present in exon 3. Certain missense mutations in exon 3 produce unstable globins and thalassemia intermedia with hemolysis in heterozygotes. Here we report two new mutations in exon 3 of the beta-globin gene. One is a single nucleotide deletion in codon 109 in a 78-year-old Lithuanian with chronic hemolytic anemia and features of thalassemia. It leads to an abnormal globin (beta Manhattan) that is elongated to 156 amino acids. The second is a CAG-CGG missense mutation at codon 127 that causes a Gln----Pro substitution (beta Houston) and a thalassemia intermedia with hemolysis in three generations of a British-American family. Although the clinical phenotypes of these two patients differed little, differences in globin-synthetic ratios were significant, presumably reflecting differences in the ability of each abnormal beta-globin to form alpha beta dimers. The paucity of high-frequency exon 3 mutations and their worldwide distribution is likely attributable to their phenotypic severity and loss of increased genetic fitness vis-a-vis malaria.
地中海贫血综合征：分子基础和产前诊断，1990 年。
影响因子：
3.6
作者：
KazazianJr,HH
通讯作者：
KazazianJr,HH
包涵体β地中海贫血的一种形式是由于β链第121位密码子处的GAA----TAA突变所致。
影响因子：
20.3
作者：
Fei,YJ;Stoming,TA;Kutlar,A;Huisman,TH;Stamatoyannopoulos,G
通讯作者：
Stamatoyannopoulos,G