Genotype-phenotype correlation and mutation spectrum of HBB gene in the Hatay province of Turkey

Year 2024, Volume: 49 Issue: 1, 40 - 46, 29.03.2024

Murat Kaçmaz Semih Aşıkovalı

https://doi.org/10.17826/cumj.1394315

Abstract

Purpose: Thalassemia carriage and hemoglobinopathies are quite common disorders in Turkey, especially in the Çukurova region, including Hatay province. Due to the high case population and genetic diversity in our region, this study aimed to investigate the genotype-phenotype correlation in the HBB gene.
Materials and Methods: The data of patients who applied to Hatay Mustafa Kemal University Medical Genetics or Hematology Clinic between January 2010 and November 2022 were evaluated retrospectively.
Results: A total of 40 (100%) cases, comprising 25 (62.5%) homozygous and 15 (37.5%) compound heterozygous genotypes, were included in the study based on the mutation profiles in the HBB gene. In the analysis of the cases, it was seen that there were 17 different variants and 22 distinct genotypes. The three most common variants identified in this study were IVS-I-6 (T>C), IVS-I-1 (G>A), and IVS-II-848 (C>A). Of the cases with homozygous genotypes, 13 (52%) had the IVS-I-6 (T>C) variant. The most frequent genotypes observed in cases with compound heterozygous genotype were IVS-I-6 (T>C)/IVS-I-110 (G>A), IVS-I-6 (T>C)/Hb Knossos, and IVS-I-110 (G>A)/-101 C>T, each in 2 (13%) cases.
Conclusion: This study provides information on the phenotypic characteristics of very rare genotypes. We think that this information will be very beneficial, especially for clinicians interested in prenatal diagnosis, preimplantation genetic diagnosis, and postnatal genetic counseling.

Keywords

Hemoglobinopathies, hemoglobin Knossos, Genetic Counseling

Türkiye'nin Hatay ilinde HBB geninin genotip-fenotip korelasyonu ve mutasyon spektrumu

Abstract

Amaç: Talasemi taşıyıcılığı ve hemoglobinopatiler, aralarında Hatay ilininde bulunduğu Çukurova bölgesi başta olmak üzere Türkiye'de oldukça yaygın görülen rahatsızlıklardır. Bölgemizdeki vaka popülasyonunun ve genetik çeşitliliğin fazla olması nedeniyle bu çalışma HBB genindeki genotip-fenotip korelasyonunu araştırmayı amaçlamaktadır.
Gereç ve Yöntem: Hatay Mustafa Kemal Üniversitesi Tıbbi Genetik veya Hematoloji Kliniğine Ocak 2010 ve Kasım 2022 arasında başvuran hastaların verileri retrospektif olarak değerlendirildi.
Bulgular: Bu çalışmaya HBB genindeki mutasyon profillerine göre 25’i (%62,5) homozigot ve 15’i (%37,5) birleşik heterozigot genotipten oluşan toplam 40 (%100) olgu dahil edildi. Olguların analizinde 17 farklı varyant ve 22 farklı genotip olduğu görüldü. En sık saptanan üç varyant IVS-I-6 (T>C), IVS-I-1 (G>A) ve IVS-II-848 (C>A) idi. Homozigot genotipli olguların 13’ünde (%52) IVS-I-6 (T>C) varyantı vardı. Birleşik heterozigot genotipli olgularda en sık görülen genotipler, her biri 2 (%13) olguda görülmek üzere IVS-I-6 (T>C)/IVS-I-110 (G>A), IVS-I-6 (T>C)/Hb Knossos ve IVS-I-110 (G>A)/-101 C>T şeklindeydi.
Sonuç: Bu çalışmada oldukça nadir görülen genotiplerin fenotipik özelliklerine dair bilgiler mevcuttur. Bu bilgilerin özellikle doğum öncesi tanı, preimplantasyon genetik tanı ve doğum sonrası genetik danışmanlıkla ilgilenen klinisyenler için oldukça faydalı olacağı görüşündeyiz.

Keywords

Hemoglobinopatiler, hemoglobin Knossos, Genetik Danışmanlık

References

• 1. Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis. 2010;5:11.
• 2. Taher AT, Musallam KM, Cappellini MD. β-Thalassemias. N Engl J Med. 2021;384:727-43.
• 3. Steinberg MH, Forget BG, Higgs DR, Weatherall DJ. Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. 2 ed. Cambridge: Cambridge University Press; 2009.
• 4. Canatan D. Thalassemias and hemoglobinopathies in Turkey. Hemoglobin. 2014;38:305-7.
• 5. Cürük MA, Arpaci A, Attila G, Tuli A, Kilinç Y, Aksoy K et al. Genetic heterogeneity of beta-thalassemia at Cukurova in southern Turkey. Hemoglobin. 2001;25:241-45.
• 6. Altay Ç. The Frequency and Distribution Pattern of ß-Thalassemia Mutations in Turkey. Turk J Haematol. 2002;19:309-15.
• 7. Yuzbasioglu Ariyurek S, Yildiz SM, Yalin AE, Guzelgul F, Aksoy K. Hemoglobinopathies in the Çukurova region and neighboring provinces. Hemoglobin. 2016;40:168-72.
• 8. Arpaci A, Gul BU, Ozcan O, Ilhan G, El C, Dirican E et al. Presentation of two new mutations in the 3'untranslated region of the β-globin gene and evaluating the molecular spectrum of thalassemia mutations in the Mediterranean region of Turkey. Ann Hematol. 2021;100:1429-38.
• 9. Aydınok Y, Oymak Y, Atabay B, Aydoğan G, Yeşilipek A, Ünal S et al. A national registry of thalassemia in Turkey: demographic and disease characteristics of patients, achievements, and challenges in prevention. Turk J Haematol. 2018;35:12-18.
• 10. Guvenc B, Canataroglu A, Unsal C, Yildiz SM, Turhan FT, Bozdogan ST et al. β-Thalassemia mutations and hemoglobinopathies in Adana, Turkey: results from a single center study. Arch Med Sci. 2012;8:411-4.
• 11. Canatan D, Vives Corrons JL, Piacentini G, Kara F, Keskinkılıç B, Tezel B et al. Immigration and screening programs for hemoglobinopathies in Italy, Spain and Turkey. Acta Biomed. 2021;92:e2021410.
• 12. Yazal Erdem A, Demir Yenigürbüz F, Pekpak E, Akıncı B, Aktekin E, Bayram C et al. Refugee children with beta-thalassemia in Turkey: Overview of demographic, socioeconomic, and medical characteristics. Pediatr Blood Cancer. 2019;66:e27636.
• 13. Tadmouri GO, Tüzmen S, Ozçelik H, Ozer A, Baig SM, Senga EB et al. Molecular and population genetic analyses of beta-thalassemia in Turkey. Am J Hematol. 1998;57:215-20.
• 14. Guzelgul F, Seydel GS, Aksoy K. β-globin gene mutations in pediatric patients with β-thalassemia in the region of Çukurova, Turkey. Hemoglobin. 2020;44:249-53.
• 15. Kurtoğlu A, Karakuş V, Erkal Ö, Kurtoğlu E. β-Thalassemia gene mutations in Antalya, Turkey: results from a single centre study. Hemoglobin. 2016;40:392-95.
• 16. Faraon R, Daraghmah M, Samarah F, Srour MA. Molecular characterization of β-thalassemia intermedia in the West Bank, Palestine. BMC Hematol. 2019;19:4.
• 17. Landrum MJ, Kattman BL. ClinVar at five years: Delivering on the promise. Hum Mutat. 2018;39:1623-30.
• 18. Azimi A, Nejati P, Tahmasebi S, Alimoradi S, Alibakhshi R. Characterization of the IVS-II-821 (A>C) (HBB: c.316-30A>C) Mutation in a β-Thalassemia Phenotype in Iran. Hemoglobin. 2019;43:23-6.
• 19. Traeger-Synodinos J, Harteveld CL, Old JM, Petrou M, Galanello R, Giordano P et al. EMQN haemoglobinopathies best practice meeting. EMQN Best Practice Guidelines for molecular and haematology methods for carrier identification and prenatal diagnosis of the haemoglobinopathies. Eur J Hum Genet. 2015;23:426-37.
• 20. Saha D, Chowdhury PK, Panja A, Pal D, Nayek K, Chakraborty G et al. Effect of deletions in the α-globin gene on the phenotype severity of β-thalassemia. Hemoglobin. 2022;46:118-23.
• 21. Kumar R, Yadav R, Mishra S, Singh MPSS, Gwal A, Bharti PK et al. Krüppel-like factor 1 (KLF1) gene single nucleotide polymorphisms in sickle cell disease and its association with disease-related morbidities. Ann Hematol. 2021;100:365-73