Hemoglobinopathy gone astray—three novel forms of α-thalassemia in Norwegian patients characterized by quantitative real-time PCR and DNA sequencing

References

• Harteveld CL, Higgs DR. Alpha-thalassaemia. Orphanet J Rare Dis. 2010;5:13.
   PubMed Web of Science ®Google Scholar
• Higgs DR. The molecular basis of α-thalassemia. Cold Spring Harb Perspect Med. 2013;3(1):a011718.
   PubMed Web of Science ®Google Scholar
• Higgs DR, Wood WG. Long-range regulation of alpha globin gene expression during erythropoiesis. Curr Opin Hematol. 2008;15(3):176–183.
   PubMed Web of Science ®Google Scholar
• Farashi S, Harteveld CL. Molecular basis of α-thalassemia. Blood Cells Mol Dis. 2018;70:43–53.
   PubMed Web of Science ®Google Scholar
• Williams TN, Weatherall DJ. World distribution, population genetics, and health burden of the hemoglobinopathies. Cold Spring Harb Perspect Med. 2012;2(9):a011692.
   PubMed Web of Science ®Google Scholar
• Chong SS, Boehm CD, Higgs DR, et al. Single-tube multiplex-PCR screen for common deletional determinants of alpha-thalassemia. Blood. 2000;95(1):360–362.
   PubMed Web of Science ®Google Scholar
• Liu YT, Old JM, Miles K, et al. Rapid detection of alpha-thalassaemia deletions and alpha-globin gene triplication by multiplex polymerase chain reactions. Br J Haematol. 2000;108(2):295–299.
   PubMed Web of Science ®Google Scholar
• Tan AS-C, Quah TC, Low PS, et al. A rapid and reliable 7-deletion multiplex polymerase chain reaction assay for alpha-thalassemia. Blood. 2001;98(1):250–251.
   PubMed Web of Science ®Google Scholar
• Harteveld CL. State of the art and new developments in molecular diagnostics for hemoglobinopathies in multiethnic societies. Int J Lab Hematol. 2014;36(1):1–12.
   PubMed Web of Science ®Google Scholar
• Traeger-Synodinos J, Harteveld CL. Advances in technologies for screening and diagnosis of hemoglobinopathies. Biomark Med. 2014;8(1):119–131.
   PubMed Web of Science ®Google Scholar
• Colosimo A, Gatta V, Guida V, et al. Application of MLPA assay to characterize unsolved α-globin gene rearrangements. Blood Cells Mol Dis. 2011;46(2):139–144.
   PubMed Web of Science ®Google Scholar
• Harteveld CL, Voskamp A, Phylipsen M, et al. Nine unknown rearrangements in 16p13.3 and 11p15.4 causing alpha- and beta-thalassaemia characterised by high resolution multiplex ligation-dependent probe amplification. J Med Genet. 2005;42(12):922–931.
   PubMed Web of Science ®Google Scholar
• Schouten JP, McElgunn CJ, Waaijer R, et al. Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res. 2002;30(12):e57.
   PubMed Web of Science ®Google Scholar
• Grimholt RM, Urdal P, Klingenberg O, et al. Rapid and reliable detection of α-globin copy number variations by quantitative real-time PCR. BMC Hematol. 2014;14(1):4.
   PubMedGoogle Scholar
• Patrinos GP, Giardine B, Riemer C, et al. Improvements in the HbVar database of human hemoglobin variants and thalassemia mutations for population and sequence variation studies. Nucleic Acids Res. 2004;32(Database issue):D537–D541.
   PubMed Web of Science ®Google Scholar
• Kent WJ, Sugnet CW, Furey TS, et al. The human genome browser at UCSC. Genome Res. 2002;12(6):996–1006.
   PubMed Web of Science ®Google Scholar
• Untergasser A, Cutcutache I, Koressaar T, et al. Primer3-new capabilities and interfaces. Nucleic Acids Res. 2012;40(15):e115.
   PubMed Web of Science ®Google Scholar
• Koressaar T, Remm M. Enhancements and modifications of primer design program Primer3. Bioinformatics. 2007;23(10):1289–1291.
   PubMed Web of Science ®Google Scholar
• den Dunnen JT, Dalgleish R, Maglott DR, et al. HGVS recommendations for the description of sequence variants: 2016 update. Hum Mutat. 2016;37(6):564–569.
   PubMed Web of Science ®Google Scholar
• Kountouris P, Lederer CW, Fanis P, et al. IthaGenes: an interactive database for haemoglobin variations and epidemiology. PLOS One. 2014;9(7):e103020.
   PubMed Web of Science ®Google Scholar
• Sherry ST, Ward MH, Kholodov M, et al. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 2001;29(1):308–311.
   PubMed Web of Science ®Google Scholar
• Landrum MJ, Lee JM, Benson M, et al. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 2018;46(D1):D1062–d1067.
   PubMed Web of Science ®Google Scholar
• Fjeld B, Sudmann-Day AA, Grimholt RM, et al. Alpha-thalassemia (manuscript in preparation). Oslo, Norway: Department of Medical Biochemistry, Oslo University Hospital; 2021.
   Google Scholar
• Sudmann-Day AA, Piehler A, Klingenberg O, et al. Six-day stability of erythrocyte and reticulocyte parameters in-vitro: a comparison of blood samples from healthy, iron-deficient, and thalassemic individuals. Scand J Clin Lab Invest. 2015;75(3):247–253.
   PubMed Web of Science ®Google Scholar
• Weaver S, Dube S, Mir A, et al. Taking qPCR to a higher level: analysis of CNV reveals the power of high throughput qPCR to enhance quantitative resolution. Methods. 2010;50(4):271–276.
   PubMed Web of Science ®Google Scholar
• D'Haene B, Vandesompele J, Hellemans J. Accurate and objective copy number profiling using real-time quantitative PCR. Methods. 2010;50(4):262–270.
   PubMed Web of Science ®Google Scholar
• Grimholt RM, Urdal P, Klingenberg O, et al. Correction to: Rapid and reliable detection of α-globin copy number variations by quantitative real-time PCR. BMC Hematol. 2019;19:13.
   PubMedGoogle Scholar
• Statistisk sentralbyrå (Statistics Norway); 2021. Available from: http://www.ssb.no/befolkning/statistikker/innvbef
   Google Scholar
• Jakobsen E, Godal HC, Kierulf P. Thalassaemia minor. Twelve patients in two Norwegian families. Acta Med Scand. 1975;197(1–2):19–25.
   PubMedGoogle Scholar
• Brantberg A, Eik-Nes SH, Roberts N, et al. Severe intrauterine anemia: a new form of epsilongammagammadeltabeta thalassemia presenting in utero in a Norwegian family. Haematologica. 2009;94(8):1157–1159.
   PubMed Web of Science ®Google Scholar
• Joly P, Pegourie B, Courby S, et al. Two new alpha-thalassemia point mutations that are undetectable by biochemical techniques. Hemoglobin. 2008;32(4):411–417.
   PubMed Web of Science ®Google Scholar
• Khajavi M, Inoue K, Lupski JR. Nonsense-mediated mRNA decay modulates clinical outcome of genetic disease. Eur J Hum Genet. 2006;14(10):1074–1081.
   PubMed Web of Science ®Google Scholar
• Eng B, Patterson M, Walker L, et al. Three new alpha-thalassemia point mutations ascertained through newborn screening. Hemoglobin. 2006;30(2):149–153.
   PubMed Web of Science ®Google Scholar
• Feng L, Gell DA, Zhou S, et al. Molecular mechanism of AHSP-mediated stabilization of alpha-hemoglobin. Cell. 2004;119(5):629–640.
   PubMed Web of Science ®Google Scholar
• Thom CS, Dickson CF, Gell DA, et al. Hemoglobin variants: biochemical properties and clinical correlates. Cold Spring Harb Perspect Med. 2013;3(3):a011858.
   PubMed Web of Science ®Google Scholar
• Wajcman H, Traeger-Synodinos J, Papassotiriou I, et al. Unstable and thalassemic alpha chain hemoglobin variants: a cause of Hb H disease and thalassemia intermedia. Hemoglobin. 2008;32(4):327–349.
   PubMed Web of Science ®Google Scholar
• Vasseur-Godbillon C, Marden MC, Giordano P, et al. Impaired binding of AHSP to alpha chain variants: Hb groene hart illustrates a mechanism leading to unstable hemoglobins with alpha thalassemic like syndrome. Blood Cells Mol Dis. 2006;37(3):173–179.
   PubMed Web of Science ®Google Scholar
• Finlayson J, Ghassemifar R, Holmes P, et al. Hb lynwood [α107(G14) (-T) (α2) HBA2:c.323delT)] in conjunction with the α(3.7) deletion produces a moderately severe α-thalassemia phenotype. Hemoglobin. 2011;35(2):142–146.
   PubMed Web of Science ®Google Scholar
• Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–424.
   PubMed Web of Science ®Google Scholar
• Finlayson J, Ghassemifar R, Holmes P, et al. α-thalassemia trait caused by frameshift mutations in exon 2 of the α2-globin gene: HBA2:c.131delT and HBA2:c.143delA. Hemoglobin. 2012;36(5):511–515.
   PubMed Web of Science ®Google Scholar
• Henderson SJ, Timbs AT, McCarthy J, et al. Ten years of routine α- and β-globin gene sequencing in UK hemoglobinopathy referrals reveals 60 novel mutations. Hemoglobin. 2016;40(2):75–84.
   PubMed Web of Science ®Google Scholar
• The Norwegian 1000 genomes project; 2017 [cited 2017 Oct 12]. Available from: http://kreftgenomikk.no/en/1000genomes/
   Google Scholar
• Nicholls RD, Fischel-Ghodsian N, Higgs DR. Recombination at the human alpha-globin gene cluster: sequence features and topological constraints. Cell. 1987;49(3):369–378.
   PubMed Web of Science ®Google Scholar
• Coelho A, Picanco I, Seuanes F, et al. Novel large deletions in the human alpha-globin gene cluster: clarifying the HS-40 long-range regulatory role in the native chromosome environment. Blood Cells Mol Dis. 2010;45(2):147–153.
   PubMed Web of Science ®Google Scholar
• Harteveld KL, Losekoot M, Fodde R, et al. The involvement of Alu repeats in recombination events at the alpha-globin gene cluster: characterization of two alphazero-thalassaemia deletion breakpoints. Hum Genet. 1997;99(4):528–534.
   PubMed Web of Science ®Google Scholar
• Jia SQ, Li J, Mo QH, et al. Alpha0 thalassaemia as a result of a novel 11.1 kb deletion eliminating both of the duplicated alpha globin genes. J Clin Pathol. 2004;57(2):164–167.
   PubMed Web of Science ®Google Scholar
• White TB, Morales ME, Deininger PL. Alu elements and DNA double-strand break repair. Mob Genet Elements. 2015;5(6):81–85.
   PubMedGoogle Scholar
• Hatton CS, Wilkie AO, Drysdale HC, et al. Alpha-thalassemia caused by a large (62 kb) deletion upstream of the human alpha globin gene cluster. Blood. 1990;76(1):221–227.
   PubMed Web of Science ®Google Scholar