Haplotypes Linked to Three Rare β-Thalassemia Mutations, Originally Reported in Tunisia

Abstract

The polymorphism of the β-globin gene haplotypes and frameworks are useful in the determination of the unicentric and multicentric origin of a mutational event. In order to improve our knowledge of the chromosomal background of the β-globin gene in three β-thalassemia (thal) mutations originally reported in Tunisia, namely codons 25/26 (+T), codon 30 (G→C) and IVS-I-2 (T→G), we have investigated 13 unrelated individuals. There were five non transfusion-dependent patients homozygous for the IVS-I-2 (T→G) mutation, five others were homozygous for the codon 30 (G→C) mutation, one was a homozygote for the codons 25/26 (+T) insertion mutation and one patient was a compound heterozygote for the codon 39 (C→T) and codon 25/26 (+T) mutations; the last patient had a β^S/codon 25/26 (+T) compound heterozygous genotype. Haplotype analysis was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based methods. The framework polymorphism was established by direct sequencing.

β-Globin gene analyses demonstrated that all IVS-I-2 (T→G) cases were associated with haplotype IX; the codon 30 (G→C) mutation was supported by haplotype I, while the codons 25/26 (+T) mutation was linked to haplotypes I and IX.

Keywords:

• Haplotypes
• β-Thalassemia (thal)
• Tunisian mutations