Rare and New Mutations of B-Globin in Azari Population of Iran, a Considerable Diversity

Overview

Journal Balkan J Med Genet

Publisher Sciendo

Specialty Genetics

Date 2023 Jun 2

PMID 37265972

Authors

F H Abbasali

K Sh Mahmoud

N Hengameh

D H Mina

D Setare

D M Hale

D M Sima

Affiliations

Soon will be listed here.

Abstract

Background: Thalassemia, as the most common single-gene genetic disorder, is related to a defect in the synthesis of one or more hemoglobin chains. More than 200 mutations have been identified in the β-globin gene. Globally, every susceptible racial group has its own specific spectrum of the common mutations that are well-known to a particular geographic region. On the other hand, varying numbers of diverse rare mutations may occur.

Materials And Methods: The subjects of the study included 2113 heterozygote or homozygote β-thalassemia cases selected among couples who participated in the Iranian national thalassemia screening program from January 2011 to November 2019. Molecular characterization of the β-thalassemia mutation was initially carried out by the amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) technique for common mutations, followed by sequencing, Gap PCR, and Multiple ligation-dependent probe amplification (MLPA) methods - in cases not detected by the ARMS-PCR.

Results: The existence of 39 rare and new point mutations and 4 large deletions were described in our cohort. Sicilian (-13,337bp) deletion, CD36/37 (-T), and CD15 TGG>TGA were encountered more often than the others in a decreasing order, in terms of frequency. The least frequent mutations/deletions were deletion from HBD exon 1 to HBB promoter, 619 bp deletion, Deletion from up HBBP1-Exon3 HBBP1 and up HBB-0.5Kb down HBB, CAP+8 C>A, CD37 (G>A), CD6 (-A), IVSI-2 (T>C), IVSII-705 T>G, and IVSII-772 (G>A). Each occurred once. Five mutations/variants were also determined which have not been reported previously in Iran.

Conclusion: According to the findings of the study, the Northwestern Iranian population displayed a wide variety of thalassemia allelic distributions. Identification of rare and new mutations in the β-thalassemia in the national population is beneficial for screening programs, genetic counseling, and prenatal diagnosis.

Citing Articles

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References

Jaripour M, Hayatigolkhatmi K, Iranmanesh V, Khadivi Zand F, Badiei Z, Farhangi H . Prevalence of β-Thalassemia Mutations among Northeastern Iranian Population and their Impacts on Hematological Indices and Application of Prenatal Diagnosis, a Seven-Years Study. Mediterr J Hematol Infect Dis. 2018; 10(1):e2018042. PMC: 6039086. DOI: 10.4084/MJHID.2018.042. View

Kuliev A, Rasulov I, Dadasheva T, Schwarz E, Rosatelli C, Saba L . Thalassaemia in Azerbaijan. J Med Genet. 1994; 31(3):209-12. PMC: 1049744. DOI: 10.1136/jmg.31.3.209. View

Mahdieh N, Rabbani B . Beta thalassemia in 31,734 cases with HBB gene mutations: Pathogenic and structural analysis of the common mutations; Iran as the crossroads of the Middle East. Blood Rev. 2016; 30(6):493-508. DOI: 10.1016/j.blre.2016.07.001. View

Birgens H, Ljung R . The thalassaemia syndromes. Scand J Clin Lab Invest. 2007; 67(1):11-25. DOI: 10.1080/00365510601046417. View

Li D, He S . Genotypes of thalassemia in children: an analysis of 30 417 cases. Zhongguo Dang Dai Er Ke Za Zhi. 2021; 23(8):841-847. PMC: 8428907. DOI: 10.7499/j.issn.1008-8830.2104035. View

Najmabadi H, Sahebjam S, Pourfarzad F, Teimourian S, Sahebjam F, Amirizadeh N . The beta-thalassemia mutation spectrum in the Iranian population. Hemoglobin. 2001; 25(3):285-96. DOI: 10.1081/hem-100105221. View

Altay C . The Frequency and Distribution Pattern of ß-Thalassemia Mutations in Turkey. Turk J Haematol. 2016; 19(2):309-15. View

Akhavan-Niaki H, Derakhshandeh-Peykar P, Banihashemi A, Mostafazadeh A, Asghari B, Ahmadifard M . A comprehensive molecular characterization of beta thalassemia in a highly heterogeneous population. Blood Cells Mol Dis. 2011; 47(1):29-32. DOI: 10.1016/j.bcmd.2011.03.005. View

Sick K, Beale D, Irvine D, Lehmann H, Goodall P, MacDougall S . Haemoglobin G Copenhagen and haemoglobin J Cambridge. Two new beta-chain variants of haemoglobin A. Biochim Biophys Acta. 1967; 140(2):231-42. DOI: 10.1016/0005-2795(67)90463-1. View

10.

Najmabadi H, Ghamari A, Sahebjam F, Kariminejad R, Hadavi V, Khatibi T . Fourteen-year experience of prenatal diagnosis of thalassemia in Iran. Community Genet. 2006; 9(2):93-7. DOI: 10.1159/000091486. View

11.

Kadhim K, Baldawi K, Lami F . Prevalence, Incidence, Trend, and Complications of Thalassemia in Iraq. Hemoglobin. 2017; 41(3):164-168. DOI: 10.1080/03630269.2017.1354877. View

12.

Gaziev D . Thalassaemia in Azerbaijan. J Med Genet. 1995; 32(3):245. PMC: 1050330. DOI: 10.1136/jmg.32.3.245. View

13.

Haghi M, Feizi A, Harteveld C, Pouladi N, Feizi M . Homozygosity for a rare beta 0-thalassemia mutation [frameshift codons 25/26 (+T)] causes beta-thalassemia intermedia in an Iranian family. Hemoglobin. 2009; 33(1):75-80. DOI: 10.1080/03630260802683377. View

14.

Cao A, Rosatelli M, Leoni G, Tuveri T, Scalas M, Monni G . Antenatal diagnosis of beta-thalassemia in Sardinia. Ann N Y Acad Sci. 1990; 612:215-25. DOI: 10.1111/j.1749-6632.1990.tb24309.x. View

15.

Galehdari H, Salehi B, Pedram M, Oraki Kohshour M . High prevalence of rare mutations in the Beta globin gene in an ethnic group in iran. Iran Red Crescent Med J. 2012; 13(5):356-8. PMC: 3371978. View

16.

Weatherall D . Phenotype-genotype relationships in monogenic disease: lessons from the thalassaemias. Nat Rev Genet. 2001; 2(4):245-55. DOI: 10.1038/35066048. View

17.

Mahdavi M, Karami H, Akbari M, Jalali H, Roshan P . Detection of Rare Beta Globin Gene Mutation [+22 5UTR(G>A)] in an Infant, Despite Prenatal Screening. Case Rep Hematol. 2013; 2013:906292. PMC: 3639694. DOI: 10.1155/2013/906292. View

18.

Arous N, Blouquit Y, Hafsia R, Bardakdjian J, Lacombe C, Rosa J . Hemoglobin kenitra alpha 2 beta 2 69 (E13) Gly----Arg. A new beta variant of elevated expression associated with alpha-thalassemia, found in a Moroccan woman. Hemoglobin. 1985; 9(1):1-9. DOI: 10.3109/03630268508996977. View

19.

Yasmeen H, Toma S, Killeen N, Hasnain S, Foroni L . The molecular characterization of Beta globin gene in thalassemia patients reveals rare and a novel mutations in Pakistani population. Eur J Med Genet. 2016; 59(8):355-62. DOI: 10.1016/j.ejmg.2016.05.016. View

20.

Rahbar S, Asmerom Y, Blume K . A silent hemoglobin variant detected by HPLC: hemoglobin City of Hope beta 69 (E13) Gly----Ser. Hemoglobin. 1984; 8(4):333-42. DOI: 10.3109/03630268408991716. View