Pirastu M, Ristaldi M S, Loudianos G, Murru S, Sciarratta G V, Parodi M I, Leone D, Agosti S, Cao A
Istituto di Ricerca sulle Talassemie e Anemie Mediterranee, Consiglio Nazionale delle Ricerche, Cagliari, Italy.
Ann N Y Acad Sci. 1990;612:90-7. doi: 10.1111/j.1749-6632.1990.tb24294.x.
This paper reviews the molecular pathology of a heterogeneous group of beta-thalassemia heterozygotes which may be referred to as atypical beta-thalassemia. This group includes four different categories of heterozygous beta-thalassemia, which are characterized, respectively, by (1) normal MCV and MCH; (2) normal Hb A2; (3) normal MCV, MCH, and Hb A2 and imbalanced globin chain synthesis only or, (4) the presence of clinical manifestations. The first group is represented by a limited proportion of double heterozygotes for alpha- and beta-thalassemia. The second group includes two categories. One category is double heterozygotes for delta- and beta-thalassemia with the delta-thalassemia mutation in cis or in trans to beta-thalassemia. A number of delta-thalassemia mutations which produce this phenotype by interacting with beta-thalassemia have been described. The other category within the second group is heterozygotes for some mild beta(+)-thalassemia mutations. Within the third group, conclusive evidence for a mutation within the beta-globin gene cluster producing the silent beta-thalassemia phenotype has been obtained solely for a C----T substitution at -101 within the CACCC box of the beta-globin gene. Possible candidates are the complex rearrangements (-T, +ATA; -T, +ATATA) found at position -530 from the cap site. In the group of thalassemic hemoglobinopathies, a series of mutations mostly located in the third exon and producing elongated or truncated molecules have been recently reported. Most of the mutations are silent at the protein level, produce inclusion bodies in peripheral erythrocytes, and show a dominant transmission pattern or occur sporadically.
本文综述了一组异质性β地中海贫血杂合子的分子病理学，这类杂合子可称为非典型β地中海贫血。该组包括四类不同的杂合性β地中海贫血，其特征分别为：（1）平均红细胞体积（MCV）和平均红细胞血红蛋白含量（MCH）正常；（2）血红蛋白A2（Hb A2）正常；（3）MCV、MCH和Hb A2正常，仅存在珠蛋白链合成不平衡，或（4）有临床表现。第一组由α和β地中海贫血的有限比例的双重杂合子代表。第二组包括两类。一类是δ和β地中海贫血的双重杂合子，其中δ地中海贫血突变与β地中海贫血呈顺式或反式。已经描述了一些通过与β地中海贫血相互作用产生这种表型的δ地中海贫血突变。第二组中的另一类是某些轻度β（+）地中海贫血突变的杂合子。在第三组中，仅在β珠蛋白基因的CACCC框内 - 101处的C→T取代获得了产生静止型β地中海贫血表型的β珠蛋白基因簇内突变的确凿证据。可能的候选突变是在帽位点 - 530处发现的复杂重排（-T，+ATA；-T，+ATATA）。在地中海贫血血红蛋白病组中，最近报道了一系列主要位于第三外显子且产生延长或截短分子的突变。大多数突变在蛋白质水平上是沉默的，在外周红细胞中产生包涵体，并显示显性遗传模式或散发性出现。
