Interaction of heterozygous β0-thalassemia and triplicated alpha globin loci in a Swiss-Spanish family

Abstract

We report a Swiss-Spanish family three members of which have the clinical picture of thalassemia intermedia. Restriction endonuclease mapping of the alpha-globin cluster and digestion with Mae I of the in vitro amplified 5' segment of the beta-globin gene shows a combination of triplicated alpha globin locus, anti-3.7 kb type, with heterozygous codon 39 C----T beta (0) thalassemic mutation. These, as well as 16 similar cases reported in the literature, permit the following conclusion: a single extra alpha-globin gene gives rise to a clinically significant degree of dyserythropoietic anemia only when it interacts with a severe beta(+) or beta(0) thalassemic mutation.

Thalassemia intermedia as a result of heterozygosis for ß0-thalassemia and <FONT FACE=Symbol>aaa</FONT>anti-3.7/<FONT FACE=Symbol>aa</FONT> genotype in a Brazilian patient

“…Although genotypically identical, six subjects showed a ß-thalassemia intermedia phenotype, while two were clinically indistinguishable from ß-thalassemia minor, implying the presence of genetic modifying factors that remained undefined. Similar data have been reported by others (1,(11)(12)(13)(14)(15).…”

Effect of α-Gene Numbers on the Expression of β-Thalassemia intermedia, β-Thalassemia and (δβ)°-Thalassemia Traits

“…Contrary to our observation, a similar genetic composition was reported to be associated with severe trait conditions by Beris et al [8]. …”

“…In contrast, triplication of the α-gene coexistent with a β-thalassemia trait increases the severity of this condition [5, 6, 7, 8, 9, 10]. However, there have been some conflicting results in the literature [11, 12, 13, 14].…”

“…However, there are conflicting results regarding the phenotypic expression of combinations of a severe heterozygous β + - or β⁰-thalassemia mutation with one additional α-gene [4, 6, 8, 11, 12, 13, 14]. …”

Association of globin gene quadruplication and heterozygous thalassemia in patients with thalassemia intermedia

“…[8][9][10]24 Other α glo- bin gene rearrangements associated with β thalassemia carrier state and resulting in thalassemia intermedia, have been reported. 25 However, the phenotype of the patients with these genetic combinations is variable and depends both on the severity of the β thalassemia allele and on the number of excess α globin genes. Recently Harteveld et al 16 described segmental duplications of the α globin gene cluster causing thalassemia intermedia in 2 subjects hetorozygotes for β thalassemia.…”