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Year : 2012  |  Volume : 55  |  Issue : 3  |  Page : 422-423
Dominant β-thalassemia - A rare entity!

Department of Pathology, Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India

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Date of Web Publication29-Sep-2012

How to cite this article:
Khera R, Singh T. Dominant β-thalassemia - A rare entity!. Indian J Pathol Microbiol 2012;55:422-3

How to cite this URL:
Khera R, Singh T. Dominant β-thalassemia - A rare entity!. Indian J Pathol Microbiol [serial online] 2012 [cited 2022 Oct 3];55:422-3. Available from:


β-thalassemias are caused by point mutations or, more rarely, deletions in the β-globin gene on chromosome 11, leading to reduced (β+ ) or absent (β0 ) synthesis of the β chains of hemoglobin. Transmission is typically autosomal recessive. Howeversome dominantly inherited β-thalassemia mutations have been described. [1],[2]

Dominant β-thalassemias are rare. In contrast to typical β-thalassemias heterozygotes which are completely asymptomatic with normal blood counts and peripheral blood film, these cases (dominant β-thalassemias) present clinically with splenomegaly, jaundice, anemia, and increased incidence of gallstones. A spectrum of molecular abnormalities including missense and nonsense mutations can lead to a dominant β-thalassemia phenotype. The common denominator of these mutations is the predicted synthesis of highly unstable β-chain variants. [3] The phenotype resembles the intermediate forms of β-thalassemia by virtue of the ineffective erythropoiesis, but there is also a variable degree of peripheral hemolysis. Gene sequencing is required for confirmation of diagnosis of dominant β-thalassemia.

In a study conducted in our department on thalassemias and hemoglobinopathies, 8 out of 62 β-thalassemia trait cases had a thalassemia intermedia phenotype with moderate anemia (8/8), jaundice (2/8), splenomegaly (3/8), and gallstones (1/8). Peripheral smear demonstrated microcytic hypochromic red cells with moderate to marked degree of anisopoikilocytosis and nucleated red cells. However, CE HPLC (Bio-rad Variant II β-Thal Short Programme) revealed high HbA2 (mean 4.5%), characteristic of β-thalassemia heterozygotes, in all the cases and thus a diagnosis of β-thalassemia trait was given [Figure 1]. Serum ferritin levels were carried out on all the eight cases to rule out iron deficiency which were found to be low in four cases while in other four cases serum ferritin levels were normal to mildly increased. A diagnosis of dominant β-thalassemia was suggested in cases with normal iron studies and molecular studies were advised for confirmation. Though molecular analysis could not be done in our cases, we propose that this entity should be considered whenever in patients presenting with thalassemia intermedia-like clinical picture, HPLC shows only elevated HbA2 and serum iron studies are normal.
Figure 1: HPLC chromatogram showing elevated HbA2 concentration of 5.4% (>4% cut off for the β-thalassemia trait) and normal HbF (0.8%)

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Unlike recessive β-thalassemia, dominant β-thalassemias are rare. It is likely that the low frequency of the dominant β-thalassemia alleles is due to the lack of positive selection that occurs in the recessive forms. [4] Awareness to this rare form of thalassemia is necessary as it might lead to diagnostic dilemma while dealing with such cases.

The vast majority of the dominant β-thalassemia alleles have been described in single families, many as de novo events. Clinically, since spontaneous mutations are common in dominant β-thalassemia, so it is also important that the disorder should be suspected in any patient with a thalassemia intermedia phenotype even if both parents are hematologically normal.

   References Top

1.Thein SL. Is it dominantly inherited β thalassaemia or just a β-chain variant that is highly unstable? Br J Haematol 1999;107:12-21.  Back to cited text no. 1
2.Thein SL. Structural Variants with a β thalassemia phenotype. In: Steinberg MH, Forget BG, Higgs DR, Nagel RL, editors. Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. Cambridge, UK: Cambridge University Press, Cambridge, UK; 2001. p. 342-55.  Back to cited text no. 2
3.Hall GW, Thein SL. Nonsense codon mutations in the terminal exon of the beta globin gene are not associated with a reduction in beta-mRNA accumulation: a mechanism for the phenotype of dominant β-thalassemia. Blood 1994;83:2031-7.  Back to cited text no. 3
4.Thein SL. Genetic modifiers of beta-thalassemia. Haematologica 2005;90:649-60.  Back to cited text no. 4

Correspondence Address:
Rachna Khera
R.No.62, Department Of Pathology, Maulana Azad Medical College, Bahadurshah Zafar Marg, New Delhi-110002
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.101770

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