A novel fusion gene and a common α0-thalassemia deletion cause hemoglobin H disease in a Chinese family

Genetic recombination has been implicated as a mechanism that drives mutagenesis in the human globin gene clusters, either as a result of unequal crossover or gene conversion. In this paper, a novel fusion gene was identified in a Chinese girl with hemoglobin H disease. The proband's father was a compound heterozygote for the common -alpha(4.2) deletion and this fusion gene, and her mother was heterozygous for the common --(SEA) deletion (--(SEA)/alpha alpha) Both her parents had a hypochromic and microcytic red cell phenotype and a normal hemoglobin level. Molecular studies revealed a compound heterozygote for the --(SEA) deletion and this novel fusion gene and the patient had the clinical features of classic hemoglobin H disease. Sequence analysis revealed that the mutant gene was the result of a fusion between the alpha 2 and psi alpha 1 genes. The recombination began at exon 3 of alpha 2 gene, crossing with exon 3 of the psi alpha 1 gene. With this recombination, the conservative 3'UTR of the alpha 2 gene was changed, and an extensive transcript with a new signal 1048 bp 3' to the terminating codon was found. The abnormal transcripts of the fusion gene read through the intergenic sequence. (C) 2013 Elsevier Inc. All rights reserved.