ISSN  2587-2362  |  E-ISSN  2618-642X
Association between HBA locus copy number gains and pathogenic HBB gene variants [Int J Med Biochem ]
Int J Med Biochem . 2021; 4(2): 91-96 | DOI: 10.14744/ijmb.2021.65477

Association between HBA locus copy number gains and pathogenic HBB gene variants

Güven Toksoy1, Nergis Akay2, Agharza Aghayev1, Volkan Karaman1, Şahin Avcı1, Tugba Kalayci1, Umut Altunoğlu1, Zeynep Karakaş2, Zehra Oya Uyguner1
1Department of Medical Genetics, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey
2Department of Pediatric Hematology-Oncology, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey

INTRODUCTION: Alpha (α) and beta (β) thalassemia are the most prevalent genetic hematological disorders. The co-occurrence of silent β-thalassemia with excess α-globin gene copies is associated with the thalassemia intermedia phenotype. This study was an investigation of the α globulin gene dosage and sequence variations in thalassemia patients.
METHODS: Multiplex ligation-dependent probe amplification and Sanger sequencing were used to identify the hemoglobin subunit alpha 1 (HBA1) and HBA2 gene alterations in 32 patients. Deletion, duplication, and other findings were analyzed in the index cases and family members.
RESULTS: Four of the 32 cases (12.5%) were found to have gross duplications. Two cases demonstrated α-globin triplication, and 2 had a quadruplicated HBA1/2 genes. Affected family members revealed genotype-phenotype correlation. In 1 patient, it was observed that quadruplicated HBA genes co-occurrence with hemoglobin subunit beta (HBB) mutation was inherited from his mother. Notably, the mother did not demonstrate any thalassemia phenotype. Further investigation showed that the mother was carrying a single copy HBA gene deletion in the trans allele that explained her clinical condition.
DISCUSSION AND CONCLUSION: This study examined the effect of increased copies of the HBA gene in HBB gene pathogenic variant carriers. The results indicated that β-thalassemia mutations with a co-occurrence of increased α-globin gene dosage is not very rare condition. Patients with clinical findings incompatible with their HBB genotypes should be investigated for small and gross α-globin gene variants in order to provide genetic counseling and prenatal diagnosis follow-up, as appropriate.

Keywords: Alpha-globin gene quadruplication, co-inheritance of HBA and HBB, multiplex ligation-dependent probe amplification, thalassemia intermedia

Güven Toksoy, Nergis Akay, Agharza Aghayev, Volkan Karaman, Şahin Avcı, Tugba Kalayci, Umut Altunoğlu, Zeynep Karakaş, Zehra Oya Uyguner. Association between HBA locus copy number gains and pathogenic HBB gene variants. Int J Med Biochem . 2021; 4(2): 91-96

Corresponding Author: Güven Toksoy, Türkiye
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