First Report of the 3'-Untranslated Region +1506 (A>C) [NM_000518.5: c.*32A>C] mutation on the β-Globin Gene in the...

The 3'-untranslated region (3'-UTR) is well known to be associated with the post-transcriptional regulation, because of the presence of important sequences that influence the fate of mRNA, and thus, in protein synthesis. The present study describes a point mutation on the β-globin 3'-UTR, +1506 (A>C) (HBB: c.*32A>C) in an Indian family during prenatal diagnosis (PND) screening of an at-risk couple. The members of the family heterozygous for this mutation presented with a typical β-thalassemia (β-thal) phenotype. The haplotype analysis of the β-globin gene cluster was determined for this mutation and observed to be linked with haplotype [- + - + + + +]. Common α-globin gene deletions, triplication, and the Xmnl polymorphism, were also looked for and found to be absent in the family. The identified HBB: c.*32A>C mutation is located in the first adenylate uridylate (AU) motif of the four AU motifs situated in the 3'-UTR region of the β-globin gene. Bioinformatics analysis revealed binding of two miRNAs, hsa-miR-451a and hsa-miR-3914, at the mutation position, possibly influencing the mRNA stability by recruiting RNA binding proteins. This is the third publication reporting the 3'-UTR +1506 (A>C) mutation worldwide and the first report of the existence of this mutation in the Indian population, emphasizing the high heterogeneity of this population.