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

GÜMRÜK, FATMA; ÜNAL CANGÜL, Şule

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

Şule ÜNAL CANGÜL, (Hacettepe Üniversitesi, Tıp Fakültesi, Pediatrik Hematoloji Anabilim Dalı, Ankara, Türkiye)

Fatma GÜMRÜK (Hacettepe Üniversitesi, Tıp Fakültesi, Pediatrik Hematoloji Anabilim Dalı, Ankara, Türkiye)

Turkish Journal of Hematology

5 0

Yıl: 2015 Cilt: 32 Sayı: 2 Sayfa Aralığı: 136 - 143 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

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

Öz:

Amaç: Alfa (α) talasemilerin farklı klinik spektrumundan etkilenen α-globin gen sayısı sorumludur. Ayrıca delesyonel olmayanmutasyonların, iki α-globin geninin birden etkilendiği büyük delesyonel mutasyonlarla kombinasyon oluşturmasının da hastalığınklinik şiddetinde etkisi bulunmaktadır.Gereç ve Yöntemler: Burada Hb H hastalarımızın (n=35) hematolojik ve mutasyonel spektrumunu sunmaktayız. Buna ekolarak, merkezimize α-globin geninde mutasyon varlığı taraması için merkezimize gönderilen ve α-globin geni mutasyonu taşıyan78 bireyin bulguları analiz edilmiştir.Bulgular: Çalışmamızda daha önce bildirilenleri destekler şekilde Hb H hastası grubunda (%62,8) ve 78 bireyde (%39,7) ensık mutasyon -α3,7 olarak bulunmuştur. Hemoglobin H hastalarımızda en sık genotipler -α3.7/--20.5; -α3,7/--26,5 ve -α3,7/--17,5 olaraksırasıyla 10 (%28,6), 6 (%17,1) ve 6 (%17,1) sıklıklarda bulunmuştur. Diğer bir küçük delesyon olan -4.2 (Asya tipi), delesyonelolmayan 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 delesyonelmutasyonların 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 HbBarts yüksek olarak ölçülmüştür. Homozigot PA-2 mutasyonu olan hastalar (α PA-2/α PA-2) ağır fenotipte Hb H hastaları olarakgözlenmiştir.Sonuç: Çalışmamız Hb H hastalığının ülkemizde nadir olmadığına ve genotipinin heterojen olduğuna işaret etmektedir.

Anahtar Kelime:

Konular: Hematoloji

Türkiye de Alfa Talasemilerin Hematolojik ve Moleküler Spektrumu: Hacettepe Deneyimi

Öz:

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 geneshave an impact on the clinical severity. The objective of this study was to analyze the hematological and molecular data of 35patients with Hb H disease from a single center in order to identify the genotypes of Hb H disease and genotype-phenotypecorrelations. 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-genescreening, 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, andseveral 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 ofone of the large deletions given above. The combinations consisting of 1 non-deletional and 1 of the large deletional types ofmutations (αTα/--) at trans loci were found to result in a more severe phenotype compared to the genotypes composed of 1 smalltrans deletion of a large deletion (-α/--). The combination of α (Cd59) and -- in trans was associated with severe phenotype andthe 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.

Anahtar Kelime:

Konular: Hematoloji

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	ÜNAL CANGÜL Ş, GÜMRÜK F (2015). The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience. , 136 - 143.
Chicago	ÜNAL CANGÜL Şule,GÜMRÜK FATMA The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience. (2015): 136 - 143.
MLA	ÜNAL CANGÜL Şule,GÜMRÜK FATMA The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience. , 2015, ss.136 - 143.
AMA	ÜNAL CANGÜL Ş,GÜMRÜK F The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience. . 2015; 136 - 143.
Vancouver	ÜNAL CANGÜL Ş,GÜMRÜK F The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience. . 2015; 136 - 143.
IEEE	ÜNAL CANGÜL Ş,GÜMRÜK F "The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience." , ss.136 - 143, 2015.
ISNAD	ÜNAL CANGÜL, Şule - GÜMRÜK, FATMA. "The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience". (2015), 136-143.

APA	ÜNAL CANGÜL Ş, GÜMRÜK F (2015). The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience. Turkish Journal of Hematology, 32(2), 136 - 143.
Chicago	ÜNAL CANGÜL Şule,GÜMRÜK FATMA The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience. Turkish Journal of Hematology 32, no.2 (2015): 136 - 143.
MLA	ÜNAL CANGÜL Şule,GÜMRÜK FATMA The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience. Turkish Journal of Hematology, vol.32, no.2, 2015, ss.136 - 143.
AMA	ÜNAL CANGÜL Ş,GÜMRÜK F The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience. Turkish Journal of Hematology. 2015; 32(2): 136 - 143.
Vancouver	ÜNAL CANGÜL Ş,GÜMRÜK F The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience. Turkish Journal of Hematology. 2015; 32(2): 136 - 143.
IEEE	ÜNAL CANGÜL Ş,GÜMRÜK F "The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience." Turkish Journal of Hematology, 32, ss.136 - 143, 2015.
ISNAD	ÜNAL CANGÜL, Şule - GÜMRÜK, FATMA. "The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience". Turkish Journal of Hematology 32/2 (2015), 136-143.