A Previously Undescribed β+ Thalassemia Mutation (HBB:c.-122T>A) Identified in a Vietnamese Family | Chapter 18 | Research Trends and Challenges in Medical Science Vol. 3

Aims: To identify thalassemias in the population living in the Thua Thien Hue Province of Central Vietnam.  Study Design: The study was performed as part of an ongoing research collaboration between Universities of Sassari and Hue. The survey included nearly 200 individuals referred to Hue Medicine and Pharmacy College and PhuVang District Hospitals for hematological and clinical evaluation. Firstlevel analysis and DNA studies were carried out to identify and define thalassemia defects. Methodology: Complete blood count was measured. Serum ferritin concentration was used to determine iron­deficiency. Hemoglobin profile was defined by IEF and CE­HPLC procedures. Identification of the β­globin genotype was carried out by PCR and nucleotide sequencing of the βglobin gene. The occurrence of deletions or duplications in the HBB and HBA cluster was investigated by the Multiplex Ligation­Dependent Probe Amplification (MLPA) analysis. To assess the impact of a novel mutation on globin synthesis a K562 cell­based luciferase reporter assay was performed. Results: Four β­globin gene mutations were found, three of which previously described. The unknown mutation affects the position ­72 from the Cap site, located in the CCAAT box of the β promoter region. The variant is not associated with remarkable changes in red blood cells indices. The level of HbA2 is slightly increased. The in vitro expression studies displayed that the mutation decreases the transcriptional activity of the β promoter by about 50%. This finding made possible to classify the mutation as a β+­thalassemic allele.  Conclusions: Although the mildness of the ­72 mutation a severe phenotype resulting from a compound heterozygous state cannot be excluded. The complexity of the clinical manifestations resulting from the assortment of different β thalassemia alleles underlines the importance of identifying new or rare β+­thalassemic alleles, particularly in countries where a wide genetic variability exists. 

Author(s) Details

Monica Pirastru
Dipartimento di Scienze Biomediche, Università di Sassari, Via Muroni 25, 07100 – Sassari (SS), Italy.  

Laura Manca
Dipartimento di Scienze Biomediche, Università di Sassari, Via Muroni 25, 07100 – Sassari (SS), Italy.

Paolo Mereu
Dipartimento di Scienze Biomediche, Università di Sassari, Via Muroni 25, 07100 – Sassari (SS), Italy.

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