title: Xmn I polymorphism associated with concomitant activation of Gγ and Aγ globin gene transcription on a β0-thalassemia chromosome.
abstract: The -158 (C→T) nucleotide change, known as Xmn I polymorphism, occurs in (G)γ-globin gene promoter, and results in elevated fetal hemoglobin (HbF). We found this mutation in cis of a β(0)-thalassemia splicing mutation. Despite the complete absence of adult HbA, the phenotype was only moderately severe with no detectable alteration of α-globin gene expression. Interestingly, the β-globin locus haplotype has not been described to bear the (G)γ promoter mutation. Using a gene-specific real-time RT-PCR approach, we found a dramatic increase of both (G)γ and (A)γ mRNA accumulated in the reticulocytes, suggesting that the (G)γ-promoter mutation, alone or in association with another genetic modification, alters in concert the transcription of both (G)γ and (A)γ. This observation is discussed in light of recent regulatory model for β-globin locus.
authors.affiliation: mRNA Metabolism in Normal and Pathological Cells, CNRS, Université Lyon 1, Villeurbanne, France.
authors.forename: Amel
authors.initials: A
authors.lastname: Haj Khelil
authors.forename: Madeleine
authors.initials: M
authors.lastname: Morinière
authors.forename: Sandrine
authors.initials: S
authors.lastname: Laradi
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Khelif
authors.forename: Pascale
authors.initials: P
authors.lastname: Perrin
authors.forename: Jemni
authors.initials: J
authors.lastname: Ben Chibani
authors.forename: Faouzi
authors.initials: F
authors.lastname: Baklouti
mesh_terms: D000328:Adult; D002648:Child; D002877:Chromosomes, Human; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005319:Fetal Hemoglobin / Q000096:biosynthesis / Q000235:genetics*; D056726:Genetic Association Studies; D056426:Genetic Loci; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012156:Reticulocytes / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014416:Tunisia; D055542:alpha-Globins / Q000096:biosynthesis / Q000235:genetics*; D055544:beta-Globins / Q000096:biosynthesis / Q000235:genetics*; D017086:beta-Thalassemia / Q000235:genetics* / Q000378:metabolism
chemical_list: D055542:alpha-Globins; D055544:beta-Globins; D005319:Fetal Hemoglobin; C028649:endodeoxyribonuclease XmnI; D015252:Deoxyribonucleases, Type II Site-Specific