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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 β 0 ‐thalassaemia
Author(s) -
So ChiChiu,
Chan Amy Y. Y.,
Tsang Stella T. Y.,
Lee Anselm C. W.,
Au WingYan,
Ma Edmond S. K.,
Chan LiChong
Publication year - 2007
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2006.06383.x
Subject(s) - genetics , microbiology and biotechnology , biology , compound heterozygosity , mutation , gene , phenotype , exon , heterozygote advantage , fusion gene , genotype
Summary Anti‐Lepore haemoglobins (Hb) are rare β δ fusion variants that arise from non‐homologous crossover during meiosis, resulting in a δ – β δ – β 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 δ ‐globin. Determination of α / β ‐mRNA ratios by quantitative real‐time polymerase chain reaction demonstrated downregulation of the β gene in cis due to the interposed β δ fusion gene. Although heterozygotes have normal red cell indices and are clinically silent, compound heterozygotes with β 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‐ β + ‐thalassaemia. Awareness of the presence of anti‐Lepore Hong Kong will help to resolve diagnostic problems in regions with significant prevalence of globin disorders.