<![CDATA[The α4.2 deletion is typically characterized as a silent mutation. The clinical impact of this mutation can vary, particularly when inherited alongside other globin gene mutations, for example co-inheritance with β-thalassemia mutations, such as βCD8 (-AA)/βᴺ. This study aims to determine the α4.2 deletion breakpoint and analyze the structural and functional impact of α-thalassemia heterozygous mutation associated with α4.2 deletion and co-inheritance of αα / -α4.2/ βCD8 (-AA) / βN on the resulting hemoglobin protein. DNA sample was sequenced using the Sanger method by 1st BASE laboratory. Sequence alignment was performed via Clustal Omega, while hemoglobin structure prediction and analysis were conducted using UCSF Chimera (Chimera-1.19) and BIOVIA Discovery Studio. The results identified the α4.2 deletion breakpoint between nucleotide 26 of the X2 box and nucleotide 347 of the X1 box. Despite the mutations, the α4.2 deletion and the αα / -α4.2/ βCD8 (-AA) / βN co-inheritance resulted in a protein structure identical to normal residues, maintaining all stabilizing interactions. Therefore, we conclude that in silico predictions indicate no major structural deviations from wild-type hemoglobin A for both the α4.2 deletion and the co-inheritance of αα/-α4.2 with βCD8 (-AA)/βN. This is consistent with the molecular nature of α-thalassemia deletions, which primarily affect globin gene dosage rather than amino acid sequence, although this observation is limited to computational analysis and has not been experimentally confirmed.]]>
