TY  - JOUR
TI  - Association between HBA locus copy number gains and pathogenic HBB gene variants
AB  - Objectives: Alpha (α) and beta (β) thalassemia are the most prevalent genetic hematological disorders. The co-occur rence of silent β-thalassemia with excess α-globin gene copies is associated with the thalassemia intermedia pheno type. 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 hemo globin subunit alpha 1 (HBA1) and HBA2 gene alterations in 32 patients. Deletion, duplication, and other findings wereanalyzed 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 triplica tion, 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) mu tation was inherited from his mother. Notably, the mother did not demonstrate any thalassemia phenotype. Furtherinvestigation showed that the mother was carrying a single copy HBA gene deletion in the trans allele that explainedher clinical condition. Conclusion: This study examined the effect of increased copies of the HBA gene in HBB gene pathogenic variant car riers. The results indicated that β-thalassemia mutations with a co-occurrence of increased α-globin gene dosage isnot very rare condition. Patients with clinical findings incompatible with their HBB genotypes should be investigatedfor small and gross α-globin gene variants in order to provide genetic counseling and prenatal diagnosis follow-up, asappropriate.
AU  - Avcı, Şahin
AU  - Toksoy, Güven
AU  - Altunoglu, Umut
AU  - KARAKAS, ZEYNEP
AU  - Aghayev, Agharza
AU  - KARAMAN, VOLKAN
AU  - UYGUNER, Zehra Oya
AU  - akay, nergis
AU  - Kalayci, Tugba
DO  - 10.14744/ijmb.2021.65477
PY  - 2021
JO  - International Journal of Medical Biochemistry
VL  - 4
IS  - 2
SN  - 2587-2362
SP  - 91
EP  - 96
DB  - TRDizin
UR  - http://search/yayin/detay/487390
ER  -