Tzetis M, Traeger-Synodinos J, Kanavakis E, Metaxotou-Mavromati A, Kattamis C
First Department of Pediatrics, Athens University, St. Sophie's Children's Hospital, Greece.
Hematol Pathol. 1994;8(1-2):25-34.
Heterozygotes for beta-thalassemia usually have raised levels of HbA2, but in Greece about 5% of beta-thalassemia carriers are observed to have normal or borderline levels. It is postulated that such cases have mild beta+ thalassemia mutations or coinheritance of delta-thalassemia. We selected 18 heterozygotes with the hematological phenotype of normal HbA2 (type 2) beta thalassemia who were negative for the delta beta Corfu mutation, and screened them for previously defined Mediterranean beta-thalassemia and delta-thalassemia mutations. The coinheritance of beta and delta-thalassemia was demonstrated in four cases with the following genotypes: in cis beta+ IVSII -n745/delta+ 27, beta 0NS39/delta 059(-A), beta+ IVSI-n110/delta 059(-A) and in trans beta+ IVSI-n6 and delta+ 27. A further nine heterozygotes had mild beta(+)-thalassemia mutations (eight with the beta+ IVSI-n6 mutation, one with the beta+ polyA (A-->G) mutation). In four heterozygotes with severe beta-thalassemia chromosomes (2 beta+ IVSI-n110, 1 beta 0 FSC-6, 1 beta 0 IVSI-n1) no known delta-thalassemia mutations were observed. One case had a delta beta deletion chromosome. These results indicate that the hematological phenotype of normal HbA2 (type 2) beta-thalassemia in Greece is genetically heterogeneous; it is mainly associated with the delta beta Corfu mutation or coinheritance of beta and delta thalassemia mutations or with very mild beta(+)-thalassemia mutations, mainly beta+ IVSI-n6. In the rare cases with severe beta-thalassemia mutations, the normal levels of HbA2 may be due to coinheritance of as yet undefined delta thalassemia mutations.
β地中海贫血杂合子通常HbA2水平升高，但在希腊，约5%的β地中海贫血携带者HbA2水平正常或处于临界值。据推测，此类病例存在轻度β+地中海贫血突变或δ地中海贫血的共遗传现象。我们选取了18名具有正常HbA2（2型）β地中海贫血血液学表型且δβ科孚突变阴性的杂合子，对他们进行先前定义的地中海β地中海贫血和δ地中海贫血突变筛查。在4例具有以下基因型的病例中证实了β和δ地中海贫血的共遗传：顺式β+IVSII -n745/δ+ 27、β0NS39/δ059(-A)、β+IVSI-n110/δ059(-A)以及反式β+IVSI-n6和δ+ 27。另外9名杂合子存在轻度β(+)-地中海贫血突变（8例为β+IVSI-n6突变，1例为β+多聚腺苷酸（A→G）突变）。在4例具有严重β地中海贫血染色体（2例β+IVSI-n110、1例β0FSC-6、1例β0IVSI-n1）的杂合子中，未观察到已知的δ地中海贫血突变。1例有δβ缺失染色体。这些结果表明，希腊正常HbA2（2型）β地中海贫血的血液学表型在遗传上具有异质性；它主要与δβ科孚突变、β和δ地中海贫血突变的共遗传或非常轻度的β(+)-地中海贫血突变（主要是β+IVSI-n6）相关。在罕见的具有严重β地中海贫血突变的病例中，HbA2水平正常可能是由于尚未明确的δ地中海贫血突变的共遗传。
