The first association of Hb Knossos: (HBB: c.82G>T) with (HBB: c.118C˃T) mutation causes thalassemia homozygous in Algerian children

Kamilia Belhadi; GribaaMoez; Hayat Djaara; OuarhlentYamina

doi:10.30574/gscbps.2020.12.1.0192

Authors

Kamilia Belhadi Biotechnology’s Laboratory of the Bioactive Molecules and the Cellular Physiopathology, Faculty of Biological Sciences, Department of Biology and Living Organisms, University of Mustapha Ben Boulaid. 53 Constantine Rd, Fesdis, Batna 05078, Algeria.
GribaaMoez Laboratory of Human Cytogenetics, Molecular Genetics and Reproductive Biology, Farhat Hached University Hospital, Sousse, Tunisia.
Hayat Djaara Biotechnology’s Laboratory of the Bioactive Molecules and the Cellular Physiopathology, Faculty of Biological Sciences, Department of Biology and Living Organisms, University of Mustapha Ben Boulaid. 53 Constantine Rd, Fesdis, Batna 05078, Algeria.
OuarhlentYamina Department of Hematology, University Hospital of Batna, Algeria.

DOI:

https://doi.org/10.30574/gscbps.2020.12.1.0192

Keywords:

Beta-thalassemia, Hb Knossos, HBB gene, Genetic Counseling, Algeria

Abstract

Beta-thalassemia is the most common disease among hemoglobinopathies in Algeria. Mutations found in Algerian beta-thalassemia patients constitute a heterogeneous group, consisting mostly of point mutations. Only in very rare cases did deletions or insertions cause affected or carrier phenotypes. Hb Knossos (HBB: c.82G> T) is a rare variant. In this study, we aimed to investigate the effect of compound heterozygosis for Hb Knossos (HBB: c.82G> T) and (HBB: c.118C˃T). To our knowledge, this is the first report of such a combination related with beta-thalassemia major phenotype in a Algerian family, we used the minisequencing assay as a rapid screening procedure to identify most common HBB genetic variants and direct DNA sequencing to detect the rare mutations of HBB gene. Heterozygous inheritance of the mutation results in severe beta-thalassemia phenotype. The proband was a 13-year-old boy when first studied. He was referred because of severe anemia. Hematological analysis of the reveals Hb 7.2 g/dl; with microcytosis of 71.1 fl, hypochromia 25 pg and the number of red blood cells is 2.9 10⁶ / mm³ . In addition, a significantly secondary thrombocytosis and leukocytosis were reported in patient. Electrophoresis of hemoglobin in an alkaline medium shows Hb A2 = 4% HbF = 65% and blood smear confirms microcytosis hypochromia, and showing the presence of many dacrocyte with hypereosinophilia.

The combination of these mutations Hb Knossos (HBB: c.82G> T) and (HBB: c.118C˃T) causes the beta-thalassemia major phenotype, and this is important for genetic counseling.

Metrics

Metrics Loading ...

References

Weatherall DJ. (1991). Thethalassemias. In: Williams JW. (ed)Haematology, 6th edn. McGraw Hill, New York.

Weatherall DJ and Clegg JB. (2001). The thalassemia syndromes. Blackwell Science, Oxford.

Belhani M. (2009). Epidemiology of homozygous β-thalassemia in Algeria. Review Algerian Hematol, 1, 22.

Bennani C, Bouhass R and Perrin-Pecontal P et al. (1994). Anthropological approach to the heterogeneity of Β-Thalassemia mutations in Northern Africa. Hum Biol, 66(3), 369–382.

Bennani C, Tamouza R and Rouabhi F et al. (1993). The spectrum of β-thalassemia in Algeria: PossibleOrigins of the molecular heterogeneity and a tentative diagnostic strategy. Br J Haematol, 84(2), 335–337.

Fessas PH, Loukopoulos D, Loutradi-Anagnostou A and Komis G. (1982). Silent P-thalassemia caused by a “silent” P-chain mutant: The pathogenesis of a syndrome of thalassemia intermedia. Br J Haematol, 51, 577, 1.

Baklouti F, Dorléac E, Morlé L, Laselve P, Peyramond D and Aubry M, et al. ( 1986). Homozygous hemoglobin Knossos (alpha 2 beta2 27(B9) Ala →Ser): a new variety of beta -thalassemia intermedia associated with delta (0)-thalassemia. Blood, 67, 957- 61.

Arous N, Galacteros Fand Fessas Pet al.(1982). Structural study of hemoglobin Knossos, beta 27 (B9) Ala leads to Ser. A new abnormal hemoglobin present as a silent beta-thalassemia. FEBS Lett, 147(2), 247-250.

Morlé L, Morlé F, Dorléac E, Baklouti F, Baudonnet C and Godet J et al. ( 1984). The association of hemoglobin Knossos and hemoglobin Lepore in an Algerian patient. Hemoglobin, 8, 229-38.

Galacteros F, Garin JD, Monplaisir N, Namoune S, Arous N and Blouquit Y, et al. (1984). Two new cases of heterozygous for hemoglobin knossos 27 Ala →Ser detected in the French west Indies and Algeria. Hemoglobin, 8, 215-28.

Olds RJ, Sura T, Jackson B, Wonke B,Hoffbrand AV andThein SL. (1991). A novel delta 0 mutation in cis with Hb Knossos: a study of different genetic interactions in three Egyptian families. Br J Hematol, 78, 430- 6.

Zahed L. (2001). The spectrum of beta-thalassemia mutations in the Arab populations. J Biomed Biotechnol, 1, 129 -32.

PhaedonFessas,DimitrisLoukopoulos,StavroulaKokkinou, YannisPapasotiriou andArisKaraklis. (1986). Hemoglobin Knossos: A Clinical, Laboratory, and Epidemiological Study. American Journal of Hematology, 21, 119-133.

Papasotiriou J, Karaklis A, Loukopoulos D andFessas Ph. (1983). Hemoglobin Knossos; Functional properties. Barcelona: 6th Meeting ISH (European and African Division), Abstract, 261.