Batı Ege Bölgesinde α-Talasemi Genotipleri ve α-Talasemi Genotip Frekansı

Abstract

Amaç: Yaygın görülen bir tek gen hastalığı olan Alfa talasemi, α-globin zincirinin kusurlu sentezi ile ortaya çıkar. Globin genlerindeki bozukluklara bağlı olarak çok geniş bir klinik spektruma yayılan bu hastalıkta çok sayıda belirlenmemiş taşıyıcı olduğu düşünülmektedir. Klinik semptomu olmayan sessiz taşıyıcılardan, rahim içinde ölüme yol açan şiddetli anemi ile kendini gösteren, çok değişken bulgulara sahip genetik bir hastalıktır. Bu çalışmada bu amaçla alfa globin gen mutasyonu sıklığının ve tiplerinin bulunması ve varyasyon saptanan bireylerdeki fenotipik etkiyi görmek amaçlandı. Gereç ve Yöntemler: HBA1 ve HBA2 genlerindeki intron bölgelerini çevreleyen tüm kodlama bölgesi sanger dizileme ile tespit edildi. Delesyonlar ve duplikasyonlar multipleks ligasyona bağımlı prob amplifikasyonu (MLPA) ile mutasyonlar tespit edildi. Bulgular: Bölgemizde en sık rastlanan mutasyon tipi olan -3,7 / (%23,18), 3.7 kb’lık delesyon çalışmamızda da en sık olarak görülürken, diğer mutasyonların dağılımı ise --3,7 (%6,82), -3,7/-- MED (%0,91), --MED (%6,82), --20,5 (3,15), --SEA (%1,36), -4,2 (%0,95), triplikasyon (%0,45) ve nükleotid değişimleri (%4,55) olarak tespit edilmiştir. Sonuç: Mevcut bilgiler ışığında genotipin fenotipe yansımasının da farklılıklar olması nedeniyle taşıyıcı bireylerin tesbit edilmesi ve genotip fenotip ilişkisinin netleştirilmesi açısından daha geniş popülasyon taramasına ihtiyaç duyulmaktadır. Toplumu alfa talasemi ve ağır klinik seyreden genetik hastalıklar hakkında bilinçlendirmek için taşıyıcı bireylere genetik danışmanlık verilmesi ve genetik çalışmalara ağırlık verilmesi bir gerekliliktir.

Keywords

• alfa talasemi
• genetik tanı
• mutasyon tipi
• mutasyon sıklığı

The Genotypes of α-Thalassemia and Genotypes Frequencies of α- Thalassemia in Western Aegean Region

Abstract

Aim: Alpha-thalassemia, a common single gene disorder, is caused by defective synthesis of the α-globin chain. It is thought to have a wide clinical spectrum due to defects in globin genes and a large number of indeterminate carriers. It is a genetic disease with highly variable findings ranging from silent carriers with no clinical symptoms to severe anemia leading to in utero death. In this study, we aimed to determine the frequency and types of alpha globin gene mutations and to observe the phenotypic effect in individuals with mutations. Material and Methods: The coding and intron regions of HBA1 and HBA2 genes were determined by Sanger sequencing. Deletions and duplications were detected by multiplex ligation-dependent probe amplification (MLPA). Results: This research shows that -3,7 / (%23.18),3.7 kb is the most common mutation type in our deletion research/analysis, and distribution of other mutations is as follows: --3,7 (%6.82), -3,7 / -- MED (%0,91), --MED (%6.82), --20,5 (3.18), --SEA (%1.36), -4,2 (%0.95). This research also demonstrates that triplication is at %0.45 and nucleotide mutation is %4.55. Conclusion: In the light of the available information, since there are differences in the reflection of genotype to phenotype, a larger population screening is needed to identify carrier individuals and to clarify the genotype-phenotype relationship. In order to raise public awareness about alpha thalassemia and genetic diseases with severe clinical course, it is a necessity to provide genetic counseling to carrier individuals and to focus on genetic studies.

Keywords

• alpha thalassemia
• genetic diagnosis
• mutation types
• mutation frequency

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