Co-Inheritance of Beta & Delta-Globin Gene (HbYialousa) Mutations in an Iranian β-Thalassemia Carrier

Atefeh Valaei, Farnaz Eghbalpour, Zahra Kainimoghaddam, Fatemeh Bayat, Maryam Taghavi Basmanj, Morteza Karimipoor, Sirous Zeinali

Kawsar Human Genetics Research Center, Tehran, Iran.
Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

DOI: 10.4236/ijcm.2012.37113                

Abstract

Introduction: Beta-thalassemia is characterized by absence or reduced synthesis of the β-globin. Carriers of β-thalas- semia, typically have microcytic hypochromic anemia and elevated hemoglobin HbA₂ and normal HbF level. On the other hand carriers of severe alpha-thalassemia also have similar CBC parameters to that of β-thalassemia with normal HbA₂ level. Co-presence of mutations in the β-globin and delta-globin genes (point mutations or deletions) usually give normal HbA₂ and elevated HbF level. We report a β-thal carrier with normal level of HbA₂ and increased level of HbF who had a point mutation in CD39 on the beta-globin gene and a point mutation in CD27 on the δ-globin gene named Hb-Yialousa. Materials & Methods: An individual with low hematological indices, normal HbA₂ and elevated HbF was referred to our center as routine premarital screening program. Mutations in the β-globin and δ-globin genes were screened using ARMS and sequencing methods. Results: The mutation in β- and δ-globin genes were identified as CD39 and CD27 (HbYialousa) respectively. No point mutation or deletion in α-globin gene was identified. Discussion: We showed that normal HBA₂ with elevated HbF level is due to co-inheritance of delta-globin gene mutation with mutation in the β-globin gene. When screening for β-thalassemia, one has to either rule out presence of α-globin gene mutation of mutation in the delta-globin gene.

Keywords

δ-Globin Gene; β-Thalassemia; HbYialousa; β-Globin Gene; CD39

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	P. Lahiry, S. A. Al-Attar and R. A. Hegele, “Understanding Beta-Thalassemia with Focus on the Indian Subcontinent & the Middle East,” The Open Hematology Journal, Vol. 2, 2008, pp. 5-13. doi:10.2174/1874276900802010005
[2]	H. Abolgha-semi, A. Amid, S. Zeinali, M. Radfar, P. Eshghi, M. Rahiminejad, et al., “Thalassemia in Iran Epidemiology, Prevention, and Management,” Journal of Pediatric Hematology/Oncology, Vol. 29, No. 4, 2007, pp. 233-238. doi:10.1097/MPH.0b013e3180437e02
[3]	D. J. Weatherall and J. B. Clegg, “The Molecular Pathology of the Thalassaemias,” 4th Edition, Wiley, Hoboken, 2008.
[4]	N. F. Olieveri, “The β-Thalassemias,” New England Journal of Medicine, Vol. 341, 1999, pp. 99-109. doi:10.1056/NEJM199907083410207
[5]	T. K. Nquyen, P. Joly, C. Bardel, M. Moulsma, N. Bonello-Palot and A. Francina, “The XmnI (G)Gamma Polymorphism Influences Hemoglobin F Synthesis Contrary to BCL11A and HBS1L-MYB SNPs in a Cohort of 57 Beta-Thalassemia Intermedia Patients,” Blood Cells, Molecules, and Diseases, Vol. 45, No. 2, 2010, pp. 124-127.
[6]	C. Garner, N. Silver, S. Best, S. Menzel, C. Martin, T. D. Spector and S. L. Thein, “Quantitative Trait Locus on Chromosome 8q Influences the Switch from Fetal to Adult Hemoglobin,” Blood, Vol. 104, No. 7, 2004, pp. 2184-2186.
[7]	S. A. Miller, D. D. Dykes and H. F. Polesky, “A Simple Salting out Procedure for Extracting DNA from Human Nucleated Cells,” Nucleic Acids Research, Vol. 16, No. 3, 1998, p. 1215. doi:10.1093/nar/16.3.1215
[8]	J. M. Old, “Detection of Mutations by the Amplification Refractory Mutation System (ARMS),” Protocols in Human Molecular Genetics, Methods in Molecular Biology, Vol. 9, 1992, pp. 77-84. doi:10.1385/0-89603-205-1:77
[9]	D. A. Koolen, W. M. Nillesen, M. H. A. Versteeg, G. F. M. Merkx, N. V. A. M. Knoers, M. Kets, S. Vermeer, C. M. A. van Ravenswaaij, C. G. de Kavel, H. G. Brunner, D. Smeets, B. B. A. de Vries and E. A. Sistermans, “Screening for Subtelomeric Rearrangements in 210 Patients with Unexplained Mental Retardation Using Multiplex Ligation Dependent Probe Amplification (MLPA),” Journal of Medical Genetics, Vol. 41, No. 12, 2004, pp. 892-899. doi:10.1136/jmg.2004.023671
[10]	S. Zeinali, S. M. Eram, S. B. Azimifar, V. Lotfi, P. Foulady and M. Masrouri, “First Report on the Co-Inheri- tance of (b) IVS I-1(G-T) Thalassemia with the (γ) CD85 [Phe-Ser](F1) (TTT>TCT)] HbA2 Etoliain in Iran,” The Hematology Journal, Vol. 91, No. 1, 2006, p. 45.
[11]	R. Alibakhshi, M. Arash, R. Akramipour, H. Nomani, M.-R. Farshchi, S. Fathollahi and M. Rezaei, “Molecular Analysis of Alpha Globin Gene Deletions among Patients with Microcytic Hypochromic Anemia in Kermanshah-Iran,” Behbood Journal, Vol. 14, No. 4, 2011, pp. 336-341.
[12]	B. H. Al-Awamy, “Thalassemia Syndromes in Saudi Arabia Meta-Analysis of Local Studies,” Saudi Medical Journal, Vol. 21, No. 1, 2000, pp. 8-17.
[13]	A. Giambona, C. Passarello, M. Vinciguerra, R. Li Muli, P. Teresi, M. Anzà, G. Ruggeri, D. Renda and A. Maggio, “Significance of Borderline Hemoglobin A2 Values in an Italian Population with a High Prevalence of β-Thalas- semia,” Haematologica, Vol. 93, No. 9, 2008, pp. 1380-1384.