RETROSPECTIVE ANALYSIS OF ALPHA GLOBIN COPY NUMBER VARIATIONS DETERMINED BY MLPA IN THE TRAKYA REGION

Öz

Objective: Alpha thalassemia is a common type of hemoglobinopathy that occurs as a result of deletions or point mutations in the alpha globin gene cluster. The molecular analysis of alpha thalassemia is challenging due to the presence of genes with high sequence similarities in alpha globin gene clusters and pseudogenes. As well as in all genetic diseases, determining the causative mutation types of alpha thalassemia and their frequencies have critical importance for accurate genetic screening and prevention strategies. Material and Method: In our study, alpha globin copy number variations determined by the Multiplex Ligation-dependent Probe Amplifcation (MLPA) method were examined retrospectively with suspicion of alpha thalassemia in 35 female and 43 male patients tested in the Genetic Diseases Diagnosis Center of the Medical Genetics Department at Trakya University Faculty of Medicine. Results: The most common deletion among our patients was the −α3.7 (35.3%), followed by the -α20.5 (10.3%) deletion. The -αSEA deletion was detected in three patients while 4 out of 78 cases were found to have the -αMED deletion. In three patients, a heterozygous large deletion and in one case HS40 regulatory region deletion were detected. In 14 (18%) of the patients, α globin triplications were detected. The -α4.2 deletion was detected in only one of our patients. Conclusion: Our study is the first to report the presence of eight different alpha globin copy number changes and 13 different alpha globin genotypes in the Trakya region.

Anahtar Kelimeler

• Alpha thalassemia
• globin
• copy number variation

TRAKYA BÖLGESİNDE MLPA İLE BELİRLENEN ALFA GLOBİN KOPYA SAYISI DEĞİŞİKLİKLERİNİN RETROSPEKTİF ANALİZİ

Öz

Amaç: Alfa talasemi, alfa globin gen kümesindeki delesyonların veya nokta mutasyonlarının bir sonucu olarak ortaya çıkan yaygın bir hemoglobinopati türüdür. Alfa talaseminin moleküler analizi, alfa globin gen kümesinde yüksek dizi benzerliklerine sahip genlerin ve psödogenlerin varlığı nedeniyle zordur. Tüm genetik hastalıklarda olduğu gibi, alfa talasemide de, altta yatan mutasyon türlerinin ve sıklıklarının belirlenmesi, doğru genetik tarama ve önleme stratejileri için kritik öneme sahiptir. Gereç ve Yöntem: Çalışmamızda, alfa talasemi şüphesiyle Trakya Üniversitesi Tıp Fakültesi Tıbbi Genetik Anabilim Dalı Genetik Hastalıklar Tanı ve Değerlendirme Merkezinde test edilen 35 kadın ve 43 erkek hastada Multipleks Ligasyon-bağımlı Prob Amplifikasyon (MLPA) yöntemiyle belirlenen alfa globin kopya sayısı varyasyonları geriye dönük olarak incelendi. Bulgular: Olgularımız arasında en sık (%35,3) saptanan delesyon −α3.7 ve ardından %10,3 görülme sıklığı ile −α20.5 delesyonu gelmekteydi. Üç olguda tüm probları kapsayan büyük delesyon, bir olguda ise HS40 düzenleyici bölgesinde delesyon saptanırken, 78 olgunun 4’ünde –αMED, üçünde ise –αSEA delesyonu saptandı. Olguların 14’ünde (%18) α globin triplikasyonları belirlendi. −α4.2 delesyonu olgularımızdan yalnızca bir tanesinde saptandı. Sonuç: Çalışmamız, Trakya bölgesinde sekiz farklı alfa globin kopya sayısı değişikliği ve 13 farklı alfa globin genotipinin varlığını bildiren ilk çalışmadır.

Anahtar Kelimeler

• Alfa talasemi
• globin
• kopya sayısı değişikliği

Kaynakça

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