1. The genetic basis of asymptomatic codon 8 frame-shift (HBB:c25_26delAA) β0-thalassaemia homozygotes
- Author
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Sule Unal, Bernard G. Forget, Nejat Akar, Martin H. Steinberg, A. Nazli Basak, Fatma Gumruk, Catherine Badens, Patrick G. Gallagher, Leonor Osorio, Serge Pissard, Nasir A. S. Al-Allawi, Roger Théberge, Andrew D. Campbell, John J. Farrell, Zhihua Jiang, Suchada Riolueang, Philippe Joly, Hong-Yuan Luo, Shengwen Huang, Katherine A. Benson, Vip Viprakasit, Lance Davis, David H.K. Chui, Departments of Medicine, Pathology and Laboratory Medicine, Boston University School of Medicine (BUSM), Boston University [Boston] (BU)-Boston University [Boston] (BU), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Genetique, UPEC (Universite' Paris Est Creteil), Laboratoire de Genetique, Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), University of Michigan [Ann Arbor], University of Michigan System, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)
- Subjects
Male ,0301 basic medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,Genes, myb ,[SDV]Life Sciences [q-bio] ,Dizygotic twin ,Quantitative Trait Loci ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,HBG2 ,Frameshift mutation ,Loss of heterozygosity ,Young Adult ,03 medical and health sciences ,Polymorphism (computer science) ,hemic and lymphatic diseases ,Fetal hemoglobin ,Diseases in Twins ,Twins, Dizygotic ,medicine ,Humans ,Frameshift Mutation ,Fetal Hemoglobin ,ComputingMilieux_MISCELLANEOUS ,Genetics ,Homozygote ,beta-Thalassemia ,Nuclear Proteins ,Beta thalassemia ,Hematology ,Middle Aged ,medicine.disease ,Molecular biology ,Repressor Proteins ,030104 developmental biology ,Female ,Carrier Proteins - Abstract
Two 21-year old dizygotic twin men of Iraqi descent were homozygous for HBB codon 8, deletion of two nucleotides (-AA) frame-shift β(0) -thalassaemia mutation (FSC8; HBB:c25_26delAA). Both were clinically well, had splenomegaly, and were never transfused. They had mild microcytic anaemia (Hb 120-130 g/l) and 98% of their haemoglobin was fetal haemoglobin (HbF). Both were carriers of Hph α-thalassaemia mutation. On the three major HbF quantitative trait loci (QTL), the twins were homozygous for G>A HBG2 Xmn1 site at single nucleotide polymorphism (SNP) rs7482144, homozygous for 3-bp deletion HBS1L-MYB intergenic polymorphism (HMIP) at rs66650371, and heterozygous for the A>C BCL11A intron 2 polymorphism at rs766432. These findings were compared with those found in 22 other FSC8 homozygote patients: four presented with thalassaemia intermedia phenotype, and 18 were transfusion dependent. The inheritance of homozygosity for HMIP 3-bp deletion at rs66650371 and heterozygosity for Hph α-thalassaemia mutation was found in the twins and not found in any of the other 22 patients. Further studies are needed to uncover likely additional genetic variants that could contribute to the exceptionally high HbF levels and mild phenotype in these twins.
- Published
- 2016