Hb Maruchi [α165 (E14) Ala>Pro; HBA1: c.196G>C]: A new thalassemia hemoglobinopathy related to the alpha1 globin gene.

ABSTRACT

OBJECTIVE: To describe a new mutation causing alpha thalassemia and its mechanism of action. DESIGN AND METHODS: The propositus was a 37-year-old man who presented maintained microcytosis without iron deficiency. Molecular characterization was undertaken using automatic sequencing after testing negative for the most frequent α-globin mutations by multiplex PCR followed by reverse-hybridization. RESULTS: The mutation is a single base substitution at codon 65 of the α1 globin gene [α65(E14) Ala>Pro; HBA1 c.196G>C] and leads to the substitution of a proline residue in the E helix. The resulting hemoglobin variant has been named Hb Maruchi. This new variant cannot be separated from Hb A by electrophoretic and chromatographic techniques. CONCLUSIONS: The substitution α65(E14) Ala>Pro; HBA1 c.196G>C causes a α-thalassemia silent associated with a very mild phenotype. The diagnosis of this type of mutation is important because it may cause alpha thalassemia if inherited with other clinically relevant HBA1/HBA2 variants.