rs1420779550

Molecular characterization of β-thalassemia in 28 individuals from 14 unrelated indigenous Belgian families identified seven different mutations in the β-globin gene, including four common Mediterranean mutations (codon 8 -AA, IVS-I-1 G→A, IVS-I-6 T→C, codon 39 C→T), two rarely described mutations (initiation codon T→C, codon 35 C→A), and one novel -CC deletion at codons 38/39 that can be detected by Ava II restriction analysis.

This study characterized polymorphic patterns of the (AT)x(T)y repeat motif at position -530 in the β-globin gene promoter among 40+ homozygous β-thalassemia patients with different mutations and ethnic backgrounds. The authors found distinct associations between specific β-globin mutations and (AT)x(T)y patterns (e.g., IVS-1-6 and codon 39 mutations associated with (AT)7(T)7, IVS-11-1 with (AT)9(T)5), and established strong linkage between (AT)9(T)5 and the Xmn I site at -158. No direct association was found between (AT)x(T)y motif variations and elevated γ-globin expression or fetal hemoglobin levels, suggesting these are common polymorphisms rather than functional regulatory variants.

Study identifies the spectrum of β-globin gene mutations causing β-thalassemia in the Portuguese population. Four common mutations (codon 39 C→T at 39%, IVS1 nt1 G→A at 26%, IVS1 nt110 G→A at 17%, IVS1 nt6 T→C at 15%) account for 97% of defects in 93 chromosomes. Two novel mutations are described: a promoter C→T substitution at position -90 in the CACCC box and a 2-bp deletion (AG) in IVS2, along with one uncommon codon 121 G→T transversion. The study enables prenatal diagnosis in 95% of at-risk couples.