title: A novel beta-delta globin gene fusion, anti-Lepore Hong Kong, leads to overexpression of delta globin chain and a mild thalassaemia intermedia phenotype when co-inherited with beta(0)-thalassaemia.
abstract: Anti-Lepore haemoglobins (Hb) are rare betadelta fusion variants that arise from non-homologous crossover during meiosis, resulting in a delta-betadelta-beta configuration. A novel anti-Lepore mutation (anti-Lepore Hong Kong) was found in two Chinese families with raised Hb A(2). Direct sequencing revealed a crossover within a 54-bp region spanning the junction of cap site (CAP) and exon 1, which predicted the production of normal delta-globin. Determination of alpha/beta-mRNA ratios by quantitative real-time polymerase chain reaction demonstrated downregulation of the beta gene in cis due to the interposed betadelta fusion gene. Although heterozygotes have normal red cell indices and are clinically silent, compound heterozygotes with beta(0) mutation in trans produce a mild thalassaemia intermedia phenotype with a markedly raised Hb A(2) level that may mimic clinically mild Hb E-beta(+)-thalassaemia. Awareness of the presence of anti-Lepore Hong Kong will help to resolve diagnostic problems in regions with significant prevalence of globin disorders.
authors.affiliation: Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong. scc@pathology.hku.hk
authors.forename: Chi-Chiu
authors.initials: CC
authors.lastname: So
authors.forename: Amy Y Y
authors.initials: AY
authors.lastname: Chan
authors.forename: Stella T Y
authors.initials: ST
authors.lastname: Tsang
authors.forename: Anselm C W
authors.initials: AC
authors.lastname: Lee
authors.forename: Wing-Yan
authors.initials: WY
authors.lastname: Au
authors.forename: Edmond S K
authors.initials: ES
authors.lastname: Ma
authors.forename: Li-Chong
authors.initials: LC
authors.lastname: Chan
mesh_terms: D000328:Adult; D001483:Base Sequence; D002648:Child; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D050939:Gene Fusion; D014644:Genetic Variation; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006443:Hemoglobin A2 / Q000378:metabolism; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006579:Heterozygote; D006723:Hong Kong; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013789:Thalassemia / Q000097:blood / Q000235:genetics*; D017086:beta-Thalassemia / Q000097:blood / Q000235:genetics
chemical_list: D017931:DNA Primers; D006455:Hemoglobins, Abnormal; D005914:Globins; D006443:Hemoglobin A2