Identification of a Novel Mutation in the β-Globin Gene 3′ Untranslated Region [+1,506 (A>C)] in a Japanese Male with a Heterozygous β-Thalassemia Phenotype

Abstract

β-Thalassemia (β-thal) is characterized by the absent or reduced production of β-globin chains. The precise molecular lesion that causes decreased β-globin synthesis in β(+)-thal is difficult to predict when mutations occur in the locus control region (LCR), the promoter, the introns or 3' untranslated regions (3'UTRs). Among them, the role of the 3'UTR of β-globin gene in mRNA stability is poorly understood, mainly due to very few cases that have mutations in this region. So far, only three mutations have been reported in the 3'UTR of β-globin gene. Although, it is speculated that some of these reported mutations could be associated with mRNA stability, the precise molecular basis still remains unclear. We report here a novel mutation in the β-globin gene 3'UTR [+1,506 (A>C)] in a 31-year-old Japanese male with hematological parameters suggestive of heterozygous β-thal. Further functional studies on this novel mutation reported here, may help in understanding of the regulation and expression of the β-globin gene and its products.

Two novel mutations in the 3′ untranslated region of the beta‐globin gene that are associated with the mild phenotype of beta thalassemia

“…Four of them are deletional in type, while the remaining are single nucleotide changes [7][8][9][10][11][12][13]. In addition to the HbVar database, a new point mutation in the 3′UTR of the b-globin gene has recently been reported [14]. Here, we describe two novel mutations located in the 3′ UTR of the b-globin gene and discuss their effects on the b-thal phenotype.…”

Compound heterozygosity of a silent beta‐thalassemia mutation at the 3′‐untranslated region (HBB: c.*132 C>T) and beta‐zero thalassemia results in thalassemia intermedia

“…Mutations in the region are generally associated with silent beta‐thalassemia with no hematologic abnormalities detected in carriers. Mutations in 3′‐UTR are rather uncommon with 18 reported mutations to date …”

A Hemizygous Deletion Within the PGK1 Gene in Males with PGK1 Deficiency

“…Variants outside the poly-A signal sequence have also been identified as causative of disease. These include the 13 bp deletion and the c.*32A>C variant in the 3 0 UTR of the bglobin mRNA (HBB gene) which result in thalassemia by affecting nuclear processing of the mRNA or by decreasing mRNA stability, respectively (Bilenoglu et al 2002;Hino et al 2012). Alternatively, similar variants that disrupt 3 0 UTR sequences may alter recruitment of trans-acting factors which regulate gene expression or modify the 3 0 UTR secondary structure, thereby leading to disease (Chen et al 2006).…”