title: A novel fusion gene and a common α(0)-thalassemia deletion cause hemoglobin H disease in a Chinese family.
abstract: 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 -α(4.2) deletion and this fusion gene, and her mother was heterozygous for the common --(SEA) deletion (--(SEA)/αα). 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 α2 and ψα1 genes. The recombination began at exon 3 of α2 gene, crossing with exon 3 of the ψα1 gene. With this recombination, the conservative 3'UTR of the α2 gene was changed, and an extensive transcript with a new signal 1048bp 3' to the terminating codon was found. The abnormal transcripts of the fusion gene read through the intergenic sequence.
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, China. hjiqing1314@yahoo.com.cn
authors.forename: Ji-Wei
authors.initials: JW
authors.lastname: Huang
authors.forename: Xuan
authors.initials: X
authors.lastname: Shang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ren
authors.initials: R
authors.lastname: Cai
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Zhang
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Wei
authors.forename: Fu
authors.initials: F
authors.lastname: Xiong
authors.forename: Xiang-Min
authors.initials: XM
authors.lastname: Xu
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D005260:Female; D017353:Gene Deletion; D050939:Gene Fusion; D006447:Hemoglobin H / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D010375:Pedigree; D014158:Transcription, Genetic; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000175:diagnosis / Q000235:genetics*
chemical_list: D055542:alpha-Globins; D006447:Hemoglobin H