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. 2015 Jun;32(2):136-43.
doi: 10.4274/tjh.2014.0200.

The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience

Şule Ünal  1 , Fatma Gümrük
Affiliations

The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience

Şule Ünal et al. Turk J Haematol. 2015 Jun.

Abstract
in English, Turkish

Objective: The spectrum of α-thalassemias correlates well with the number of affected α-globin genes. Additionally, combinations of the several non-deletional types of mutations with a large trans deletion comprising the 2 α-globin genes have an impact on the clinical severity. The objective of this study was to analyze the hematological and molecular data of 35 patients with Hb H disease from a single center in order to identify the genotypes of Hb H disease and genotype-phenotype correlations.

Materials and methods: Herein, we report the hematological and mutational spectrum of patients with Hb H disease (n=35). Additionally, genotypes of α-gene mutations of 78 individuals, who were referred to our institution for α-gene screening, were analyzed.

Results: Supporting the previous data from Turkey, -α3.7 was the most common mutation among patients with Hb H disease (62.8%) and in the other 78 subjects (39.7%). Of the patients with Hb H disease, the most common genotypes were -α3.7/--20.5, -α3.7/--26.5, and -α3.7/--17.5 in 10 (28.6%), 6 (17.1%), and 6 (17.1%) patients, respectively. Another small deletion, -4.2 alpha, and several non-deletional types of α-gene mutations, namely α (-5nt): IVS-I donor site (GAG.GTG.AGG->GAG.G-----); α (PA-2): AATAAA>AATGGA, and α (cd59): GGC->GAC, were found to be associated with Hb H disease when present at trans loci of one of the large deletions given above. The combinations consisting of 1 non-deletional and 1 of the large deletional types of mutations (αTα/--) at trans loci were found to result in a more severe phenotype compared to the genotypes composed of 1 small trans deletion of a large deletion (-α/--). The combination of α (Cd59) and -- in trans was associated with severe phenotype and the disease was associated with an increase in Hb Bart's level with null Hb H. In spite of the presence of 2 intact α-globin genes, homozygosity for PA-2 mutation resulted in severe Hb H disease.

Conclusion: This study indicated that Hb H disease is not rare in Turkey and its genotype is quite heterogeneous.

Amaç: Alfa (α) talasemilerin farklı klinik spektrumundan etkilenen α-globin gen sayısı sorumludur. Ayrıca delesyonel olmayan mutasyonların, iki α-globin geninin birden etkilendiği büyük delesyonel mutasyonlarla kombinasyon oluşturmasının da hastalığın klinik şiddetinde etkisi bulunmaktadır. Gereç ve Yöntemler: Burada Hb H hastalarımızın (n=35) hematolojik ve mutasyonel spektrumunu sunmaktayız. Buna ek olarak, merkezimize α-globin geninde mutasyon varlığı taraması için merkezimize gönderilen ve α-globin geni mutasyonu taşıyan 78 bireyin bulguları analiz edilmiştir. Bulgular: Çalışmamızda daha önce bildirilenleri destekler şekilde Hb H hastası grubunda (%62,8) ve 78 bireyde (%39,7) en sık mutasyon -α3,7 olarak bulunmuştur. Hemoglobin H hastalarımızda en sık genotipler -α3.7/--20.5; -α3,7/--26,5 ve -α3,7/--17,5 olarak sırasıyla 10 (%28,6), 6 (%17,1) ve 6 (%17,1) sıklıklarda bulunmuştur. Diğer bir küçük delesyon olan -4.2 (Asya tipi), delesyonel olmayan α-globin mutasyonları α (-5nt): IVS-I donor site (GAG.GTG.AGG->GAG.G-----); α (PA-2): AATAAA>AATGGA ve α (cd59): GGC->GAC; translarında büyük delesyonel bir mutasyon bulunduğunda Hb H hastalığına neden olduğu görülmüştür. Delesyonel olmayan mutasyonla büyük delesyonel tipte mutasyonların kombinasyonlarının (αTα/--), sadece delesyonel mutasyonların kombinasyonları sonucu gelişen Hb H hastalarına göre kliniklerinin daha şiddetli olduğu gözlenmiştir (-α/--). α(Cd59) ve -- trans birlikteliğinde, (α (Cd59)/--), daha ağır bir fenotip izlenmiştir ve bu durumda Hb H bulunmayıp, hastada Hb Bart’s yüksek olarak ölçülmüştür. Homozigot PA-2 mutasyonu olan hastalar (α PA-2/α PA-2) ağır fenotipte Hb H hastaları olarak gözlenmiştir. Sonuç: Çalışmamız Hb H hastalığının ülkemizde nadir olmadığına ve genotipinin heterojen olduğuna işaret etmektedir.

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Conflict of interest statement

Conflict of Interest Statement

The authors of this paper have no conflicts of interest, including specific financial interests, relationships, and/or affiliations relevant to the subject matter or materials included.

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  • Hemoglobin H Disease in Turkey: Experience from Eight Centers.
    Ünal S, Oktay G, Acıpayam C, İlhan G, Gali E, Celkan T, Bay A, Malbora B, Akar N, Oymak Y, Toptaş T. Ünal S, et al. Turk J Haematol. 2016 Mar 5;33(1):56-9. doi: 10.4274/tjh.2014.0461. Epub 2015 Aug 6. Turk J Haematol. 2016. PMID: 26376738 Free PMC article.

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