First Spanish Case Of Thalassemia Major Due to a Compound Heterozygosity for the IVS-II-848 (C→A) And Codon 39 (C→T) Mutations Of The β-Globin Gene

Abstract

This report describes the first case in Spain of a severe form of β-thalassemia (thal) due to a compound heterozygosity for the IVS-II-848 (C→A) and the nonsense codon 39 (C→T) mutations. Five members of a family from Cadiz (southern Spain) were studied. The proband was an 8-year-old girl diagnosed as anemic at the age of 13 months. Her father had the codon 39 (C→T) mutation and her mother the C→A change at nucleotide (nt) 848 of IVS-II. Haplotype analysis showed that the proband was a compound heterozygote for haplotypes I [+ − − − − + +] and VII [+ − − − − − +]. This is the first description in Spain of the IVS-II-848 (C→A) mutation. It appears, from restriction fragment length polymorphism (RFLP) analysis, that this mutation has a different origin in the various populations, where it was found.

This observation shows that in this case the association of a β⁰- and a β⁺-thal mutation does not lead to a thalassemia intermedia but to a severe thalassemia with very low hemoglobin (Hb) levels. From a therapeutic point of view, early introduction of a transfusion regimen may improve the clinical picture of these children, allowing for better development and growth.

Keywords:

• Thalassemia major
• β⁺/β⁰-Thalassemia (thal) [IVS-II-848(C→A)/codon 39 (C→T)]
• Haplotype(s)