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

Abstract

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.

Keywords:

• Adenylate uridylate (AU) motifs
• β-globin gene
• β-thalassemia (β-thal)
• 3′-untranslated region (3′-UTR)

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study was supported by the National Health Mission West Bengal (WBNHM), Health and Family Welfare Department, Government of West Bengal, India.