Hb Iberia [α104(G11)Cys → Arg,TGC>CGC (α2) (HBA2:c.313T>C)], a New α-Thalassemic Hemoglobin Variant Found in the Iberian Peninsula: Report of Six Cases

Abstract

We report a new structural defect of the α2-globin chain presenting with moderate microcytic hypochromic anemia, in six individuals from three unrelated families, living in Portugal and Spain. α-Globin gene deletions were ruled out by gap-polymerase chain reaction (gap-PCR) and multiplex ligation-dependent probe amplification (MLPA). Direct sequencing of the α2-globin gene revealed a substitution of codon 104 [α104(G11)Cys→Arg, TGC>CGC (α2) (HBA2:c.313T>C)]. This new variant, not detectable by high performance liquid chromatography (HPLC) or electrophoresis, was called Hb Iberia, as it was observed for the first time in families from the Iberian Peninsula.

Although the mutant allele is transcribed, as indicated by the balanced mRNA α/β ratio, the abnormal α2 chain could not form a stable tetramer as the cysteine and arginine residues, located at the α1β1 contact, differ in size, charge and hydrophobicity.

Hb Iberia is the third mutation described at codon 104 on the α-globin genes, namely, Hb Sallanches (α2, TGC>TAC) and Hb Oegstgeest (α1, TGC>AGC), also characterized as unstable hemoglobins (Hbs), present on an α-thalassemic phenotype.

• Hb Iberia
• α-Thalassemia (α-thal)
• α1β1 Contact
• Unstable hemoglobin (Hb)

ACKNOWLEDGMENTS

We are grateful to Dr. Piero C. Giordano (Hemoglobinopathies Laboratory, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands) for scientific advice and for revising this manuscript.

Declaration of Interest

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