The molecular basis of β-thalassemia

Cold Spring Harbor Perspectives in Medicine

Volumn 3, Issue 5, 2013, Pages

  Thein, Swee Lay ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

HEMOGLOBIN BETA CHAIN; RNA;

BETA THALASSEMIA; DOMINANT GENE; GENE DELETION; GENETIC TRANSCRIPTION; GENETICS; HUMAN; MUTATION; RECESSIVE GENE; REVIEW; START CODON; STOP CODON;

BETA-GLOBINS; BETA-THALASSEMIA; CODON, INITIATOR; CODON, TERMINATOR; GENE DELETION; GENES, DOMINANT; GENES, RECESSIVE; HUMANS; MUTATION; RNA; TRANSCRIPTION, GENETIC;

EID: 84878995335     PISSN: None     EISSN: 21571422     Source Type: Journal    
DOI: 10.1101/cshperspect.a011700     Document Type: Article

References (109)

1. Adams J.G.I., Boxer LA, Baehner RL, Forget BG, Tsistrakis GA, Steinberg MH. 1979. Hemoglobin Indianapolis (β112[G14] Arginine). An unstable β-chain variant producing the phenotype of severe β-thalassemia. J Clin Invest 63: 931-938.
2. Andersson B.A., Wering ME, Luo HY, Basran RK, Steinberg MH, Smith HP, Chui DH. 2007. Sickle cell disease due to compound heterozygosity for Hb S and a novel 7.7-kb β-globin gene deletion. Eur J Haematol 78: 82-85.
3. Arjona S.N., Maldonado Eloy-Garcia J, Gu L-H, Smetanina NS, Huisman THJ. 1996. The dominant β-thalassaemia in a Spanish family is due to a frameshift that introduces an extra CGG codon (1/4arginine) at the 50 end of the second exon. Br J Haematol 93: 841-844.
4. Badens C., Mattei MG, Imbert AM, Lapoumérouliee C, Martini N., Michel G, Lena-RussoD. 2002. A novel mechanism for thalassaemia intermedia. Lancet 359: 132-133.
5. Baiget M., Gomez Pereira C, Jue DL, Johnson MH, McGuffey JE, Moo-PennWF. 1986. A case of hemoglobin Indianapolis [β112(G14) Cys → Arg] in an individual from Cordoba, Spain. Hemoglobin 10: 483-494.
6. Berg P., Mittleman M, Elion J, Labie D, Schechter AN. 1991. Increased protein binding to a 2530 mutation of the human β-globin gene associatedwith decreased β-globin synthesis. Am J Hematol 36: 42-47.
7. Beris P., Miescher PA, Diaz-Chico JC, Han IS, Kutlar A, Hu H., Wilson JB, Huisman THJ. 1988. Inclusion-body β-thalassemia trait in a Swiss family is caused by an abnormal hemoglobin (Geneva) with an altered and extended β-chain carboxy-terminus due to a modification in codon β114. Blood 72: 801-805.
8. Blacklock H.A., Case J, Chan T, Raizis T, Doocey R, Fellowes A., Royle G, Jackson S, Brennan S, George P. 2005. Novel sequence insertion in a Maori patient with transfusion-dependent β-thalassaemia. Br J Haematol 131: 400-402.
9. Bunn H.F., Forget BG. 1986. Hemoglobin: Molecular, genetic and clinical aspects. W.B. Saunders Company, Philadelphia, PA.
10. + thalassemia: Aberrant splicing results from a single point mutation in an intron. Cell 27: 289-298.
11. Cantor AB. 2005. GATAtranscription factors in hematologic disease. Int J Hematol 81: 378-384.
12. Chakalova L., Osborne CS, Dai YF, Goyenechea B, Metaxotou-Mavromati A., Kattamis A, Kattamis C, Fraser P. 2005. The Corfu dβ thalassemia deletion disrupts γ-globin gene silencing and reveals post-transcriptional regulation of HbF expression. Blood 105: 2154-2160.
13. Chang J.G., TsaiWC, Chong IW, Chang CS, Lin CC, Liu TC. 2008. β-thalassemia major evolution from β-thalassemia minor is associated with paternal uniparental isodisomy of chromosome 11p15. Haematologica 93: 913-916.
14. Cheng T.C., Orkin SH, Antonarakis SE, Potter MJ, Sexton JP, Giardina P.J.V., Li A, Kazazian HHJ. 1984. β-thalassemia in Chinese: Use of in-vivo RNA analysis and oligonucleotide hybridization in systematic characterization of molecular defects. Proc Natl Acad Sci 81: 2821.
15. Codrington J.F., LiH-W, Kutlar F, Gu L-H, Ramachandran M, Huisman THJ. 1990. Observations on the levels of Hb A2 in patients with different β-thalassemia mutations and a d chain variant. Blood 76: 1246-1249.
16. Coleman M.B., Steinberg MH, Adams JG III. 1991. Hemoglobin Terre Haute arginine β106. J Biol Chem 266: 5798-5800.
17. Craig J.E., Kelly SJ, Barnetson R, Thein SL. 1992. Molecular characterization of a novel 10.3 kb deletion causing βthalassaemia with unusually high Hb A2. Br J Haematol 82: 735-744.
18. Çürük MA, Molchanova TP, Postnikov YV, Pobedimskaya DD, Liang R, Baysal E, Kolodey S, Smetanina NS, Tokarev Y.N., Rumyantsev AG, et al. 1994. β-Thalassemia alleles and unstable hemoglobin types among Russian pediatric patients. Am J Hematol 46: 329-332.
19. De Biasi R, Spiteri D, Caldora M, Iodice R, Pucci P, Malorni A., Ferranti P, Marino G. 1988. Identification by fast atom bombardment mass spectrometry on Hb Indianapolis [b112(G14)Cys → Arg] in a family from Naples, Italy. Hemoglobin 12: 323-336.
20. de Castro CM, Devlin B, Fleenor DE, Lee ME, Kaufman RE. 1994. A novel β-globin mutation, β Durham-NC [β114 Leu → Pro], produces a dominant thalassemia-like phenotype. Blood 83: 1109-1116.
21. Dobkin C., Pergolizzi RG, Bahre P, Bank A. 1983. Abnormal splice in a mutant β-globin gene not at the site of a mutation. Proc Natl Acad Sci 80: 1184.
22. Efremov GD. 2007. Dominantly inherited β-thalassemia. Hemoglobin 31: 193-207.
23. Faustino P., Osó rio-Almeida L, Romão L, Barbot J, Fernandes B., Justiça B, Lavinha J. 1998. Dominantly transmitted β-thalassaemia arising from the production of several aberrant mRNA species and one abnormal peptide. Blood 91: 685-690.
24. Fei Y.J., Stoming TA, Kutlar A, Huisman TH, Stamatoyannopoulos G. 1989. One form of inclusion body βthalassemia is due to a GAA →TAA mutation at codon 121 of the β chain. Blood 73: 1075-1077.
25. Forget BG. 2001. Molecular mechanisms of β thalassemia. In Disorders of hemoglobin: Genetics, pathophysiology, and clinical management (ed. Steinberg MH, Forget BG, Higgs D.R., Nagel RL), pp. 252-276. Cambridge University Press, Cambridge, UK.
26. Fucharoen S., Fucharoen G, Fukumaki Y, Nakayama Y, Hattori Y., Yamamoto K, Ohba Y. 1990a. Three-base deletion in exon 3 of the β-globin gene produced a novel variant (β Gunma) with a thalassemia-like phenotype. Blood 76: 1894-1896.
27. Fucharoen S., Kobayashi Y, Fucharoen G, Ohba Y, Miyazono, Fukumaki Y., Takaku F. 1990b. A single nucleotide deletion in codon 123 of the β-globin gene causes an inclusion body β-thalassaemia trait: A novel elongated globin chain βMakabe. Br J Haematol 75: 393-399.
28. Galanello R., Melis MA, Podda A, Monne M, Persey L, Loudianos G., Cao A, Pirastu M, Piga A. 1990. Deletion d-thalassemia: The 7.2 kb deletion of Corfu dβ-thalassemia in a non-β-thalassemia chromosome. Blood 75: 1747-1749.
29. Galanello R., Perseu L, Perra C, Maccioni L, Barella S, Longinotti M., Cao A, Cazzola M. 2004. Somatic deletion of the normal β-globin gene leading to thalassaemia intermedia in heterozygous β-thalassaemic patients. Br J Haematol 127: 604-606.
30. Giardine B., Borg J, Higgs DR, Peterson KR, Philipsen S, Maglott D., Singleton BK, Anstee DJ, Basak AN, Clark B., et al. 2011. Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach. Nat Genet 43: 295-301.
31. Gilman JG. 1987. The 12.6 kilobase DNA deletion in Dutch β0-thalassaemia. Br J Haematol 67: 369-372.
32. +-thalassemia gene activating a cryptic splice site in β-globin RNA coding sequence. Proc Natl Acad Sci 80: 2318.
33. Gonzalez-Redondo JM, Stoming TA, Kutlar A, Kutlar F, Lanclos K.D., Howard EF, Fei YJ, Aksoy M, Altay C, Gurgey A., et al. 1989. A C → T substitution at nt 2101 in a conserved DNA sequence of the promoter region of the β-globin gene is associated with "silent" β-thalassemia. Blood 73: 1705-1711.
34. Grosveld F., van Assendelft GB, Breaves DR, Kollias G. 1987. Position-independent, high-level expression of the human γ-globin gene in transgenic mice. Cell 51: 975-985.
35. HallGW, Thein SL. 1994. Nonsense codon mutations in the terminal exon of the β-globin gene are not associated with a reduction in β-mRNA accumulation: A mechanism for the phenotype of dominant β-thalassemia. Blood 83: 2031-2037.
36. Hall G.W., Franklin IM, Sura T, Thein SL. 1991. A novel mutation (nonsense β127) in exon 3 of the β-globin gene produces a variable thalassaemia phenotype. Br J Haematol 79: 342-344.
37. Hamid M., Akbari MT. 2011. A 13-bp deletion in the 30 untranslated region of the β-globin gene causes β-thalassemia major in compound heterozygosity with IVSII-1 mutation. Med Princ Pract 20: 488-490.
38. Hattori Y., Yamashiro Y, Ohba Y, Miyaji T, Morishita M, Yamamoto K., Yamamoto K, Narai S, Kimura A. 1991. A new β-thalassemia mutation (initiation codon ATG → GTG) found in the Japanese population. Hemoglobin 15: 317.
39. Ho P.J., Rochette J, Fisher CA, Wonke B, Jarvis MK, Yardumian A., Thein SL. 1996. Moderate reduction of β globin gene transcript by a novel mutation in the 5′ untranslated region: A study of its interaction with other genotypes in two families. Blood 87: 1170-1178.
40. Ho P.J., Wickramasinghe SN, Rees DC, Lee MJ, Eden A, Thein SL. 1997. Erythroblastic inclusions in dominantly inherited β thalassaemias. Blood 89: 322-328.
41. Huang S-C, Benz EJJ. 2001. Posttranscriptional factors influencing the hemoglobin content of the red cells. In Disorders of hemoglobin: Genetics, pathophysiology, and clinical management (ed. Steinberg MH, Forget BG, Higgs D.R., Nagel RL), pp. 252-276. Cambridge University Press, Cambridge, UK.
42. Huang S-Z, Wong C, Antonarakis SE, Ro-Lein T, Lo WHY, Kazazian HHJ. 1986. The same TATA box β-thalassemia mutation in Chinese and US Blacks: Another example of independent origins of mutation. Hum Genet 74: 162-164.
43. Huisman THJ. 1997. Levels of Hb A2 in heterozygotes and homozygotes for β-thalassemia mutations: Influence of mutations in the CACCC and ATAAA motifs of the βglobin gene promoter. Acta Haematol 98: 187-194.
44. Humphries R.K., Ley TJ, AnagnouNP, BaurAW, NienhuisAW. 1984. β0-39 thalassemia gene: A premature termination codon causes β-mRNA deficiency without affecting cytoplasmic β-mRNA stability. Blood 64: 23-32.
45. Isken O., Maquat LE. 2007. Quality control of eukaryotic mRNA: Safeguarding cells from abnormal mRNA function. Genes Dev 21: 1833-1856.
46. Jankovic L., Efremov GD, Josifovska O, Juricic D, Stoming TA, Kutlar A, Huisman THJ. 1990. An initiation codon mutation as a cause of a β0-thalassemia. Hemoglobin 14: 169.
47. Kazazian H.H.J., Orkin SH, Boehm CD, Goff SC, Wong C, Dowling C.E., Newburger PE, Knowlton RG, Brown V, Donis-Keller H. 1986. Characterisation of a spontaneous mutation to a β-thalassaemia allele. Am J Human Genet 38: 860-867.
48. Kazazian H.H.J., Dowling CE, Hurwitz RL, Coleman M, Stopeck A., Adams JGI. 1992. Dominant thalassemialike phenotypes associated with mutations in exon 3 of the β-globin gene. Blood 79: 3014-3018.
49. Kimberland M.L., Divoky V, Prchal J, Schwahn U, Berger W, Kazazian HH Jr. 1999. Full-length human L1 insertions retain the capacity for high frequency retrotransposition in cultured cells. Hum Mol Genet 8: 1557-1560.
50. Kioussis D., Vanin E, de Lange T, Flavell RA, Grosveld FG. 1983. β-globin gene inactivation by DNA translocation in γβ-thalassaemia. Nature 306: 662-666.
51. Kobayashi Y., Fukumaki Y, Komatsu N, Ohba Y, Miyaji T, Miura Y. 1987. A novel globin structural mutant, Showa-Yakushiji (β110 Leu-Pro) causing a β-thalassemia phenotype. Blood 70: 1688-1691.
52. Kulozik A., Yarwood N, Jones RW. 1988. The Corfu dβ0 thalassemia: A small deletion acts at a distance to selectively abolish β globin gene expression. Blood 71: 457-462.
53. Lam V.M.S., Xie SS, Tam JWO, Woo YK, Gu YL, Li AMC. 1990. A new single nucleotide change at the initiation codon (ATG → AGG) identified in amplified genomic DNA of a Chinese β-thalassemic patient. Blood 75: 1207-1208.
54. Li D.Z., Liao C, Li J. 2009. A novel β-thalassemic allele due to a thirteen nucleotide deletion: Codons 54-58 (-T ATG GGC AAC CCT). Ann Hematol 88: 799-801.
55. Maragoudaki E., Kanavakis E, Trager-Synodinos J, Vrettou C, Tzetis M., Metxotou-Mavrommati A, Kattamis C. 1999. Molecular, haematological and clinical studies of the 2101 C → Tsubstitution in the β-globin gene promoter in 25 β-thalassaemia intermedia patients and 45 heterozygotes. Br J Haematol 107: 699-706.
56. Moi P., Faa V, Marini MG, Asunis I, Ibba G, Cao A, Rosatelli MC. 2004. A novel silent β-thalassemia mutation in the distal CACCC box affects the binding and responsiveness to EKLF. Br J Haematol 126: 881-884.
57. Metherall J.E., Collins FS, Pan J, Weissman SM, Forget BG. 1986. β0 thalassemia caused by a base substitution that creates an alternative splice acceptor site in an intron. EMBO J 5: 2551-2557.
58. Murru S., Loudianos G, Deiana M, Camaschella C, Sciarratta GV, Agosti S, Parodi MI, Cerruti P, Cao A, Pirastu M. 1991. Molecular characterization of β-thalassemia intermedia in patients of Italian descent and identification of three novel β-thalassemia mutations. Blood 77: 1342-1347.
59. Murru S., Loudianos G, Porcu S, Sciarratta GV, Agosti S, Parodi M.I., Cao A, Pirastu M. 1992. A β-thalassaemia phenotype not linked to the β-globin cluster in an Italian family. Br J Haematol 81: 283-287.
60. Nagy E., Maquat LE. 1998. A rule for termination-codon position within intron-containing genes:When nonsense affects RNA abundance. Trends Biochem Sci 23: 198-199.
61. Ohba Y., Hattori Y, Harano T, Harano K, Fukumaki Y, Ideguchi H. 1997. β-Thalassemia mutations in Japanese and Koreans. Hemoglobin 21: 191-200.
62. Olds R.J., Sura T, Jackson B, Wonke B, Hoffbrand AV, Thein SL. 1991. A novel d0 mutation in cis with Hb Knossos: A study of different genetic interactions in three Egyptian families. Br J Haematol 78: 430-436.
63. Öner R., Öner C., Wilson JB, Tamagnini GP, Ribeiro LML, Huisman THJ. 1991. Dominant β-thalassaemia trait in a Portuguese family is caused by a deletion of (G) TGGCTGGTGT(G) and an insertion of (G)GCAG(G) in codons 134, 135, 136 and 137 of the β-globin gene. Br J Haematol 79: 306.
64. Orkin S.H., Kazazian HHJ, Antonarakis SE, Goff SC, Boehm C.D., Sexton JP, Waber PG, Giardina PJV. 1982a. Linkage of β-thalassaemia mutations and β-globin gene polymorphisms with DNA polymorphisms in human βglobin gene cluster. Nature 296: 627-631.
65. Orkin S.H., Kazazian HHJ, Antonarakis SE, Ostrer H, Goff S.C., Sexton JP. 1982b. Abnormal RNA processing due to the exon mutation of βE-globin gene. Nature 300: 768-769.
66. Orkin S., Antonarakis S, Loukopoulos D. 1984. Abnormal processing of βKnossos RNA. Blood 64: 311-313.
67. Orkin S.H., Cheng T-C, Antonarakis SE, Kazazian HHJ. 1985. Thalassemia due to a mutation in the cleavagepolyadenylation signal of the human β-globin gene. EMBO J 4: 453-456.
68. Pacheco P., Peres MJ, Faustino P, Pischedda C, Gonçalves J, Carvajales-Ramos M, Seixas T, Martins MC, Moi P, Lavinha J. 1995. β-thalassaemia unlinked to the β-globin gene interacts with sickle-cell trait in a Portuguese family. Br J Haematol 91: 85-89.
69. Park S.S., Barnetson R, Kim SW, Weatherall DJ, Thein SL. 1991. A spontaneous deletion of b33/34 Val in exon 2 of the b globin gene (Hb Korea) produces the phenotype of dominant β thalassaemia. Br J Haematol 78: 581.
70. Perseu L., Satta S, Moi P, Demartis FR, Manunza L, Sollaino M.C., Barella S, Cao A, Galanello R. 2011. KLF1 gene mutations cause borderline HbA2. Blood 118: 4454-4458.
71. Podda A., Galanello R, Maccioni L, Melis MA, Rosatelli C, Perseu L., Cao A. 1991. Hemoglobin Cagliari (β60[E4] VAL → Glu): A novel unstable thalassemic hemoglobinopathy. Blood 77: 371-375.
72. Prehu C., Pissard S, Al-Sheikh M, Le Niger C, Bachir D, Galacteros F., Wajcman H. 2005. Two French Caucasian families with dominant thalassemia-like phenotypes due to hyper unstable hemoglobin variants: Hb Sainte Seve [codon 118 (-T)] and codon 127 [CAG → TAG (Gln → stop]). Hemoglobin 29: 229-233.
73. Ristaldi M.S., Pirastu M, Murru S, Casula L, Loudianos G, Cao A., Sciarratta GV, Agosti S, Parodi MI, Leone D, et al. 1990. A spontaneous mutation produced a novel elongated β-globin chain structural variant (Hb Agnana) with a thalassemia-like phenotype. Blood 75: 1378-1380.
74. Ristaldi M.S., Casula S, Porcu S, Cao A. 2001. Normal d globin gene sequence in carrier of the silent-101 (C-T) β-thalassemia mutation with normal HbA2 level. Am J Hematol 67: 58.
75. Romao L., Inacio A, Santos S, Avila M, Faustino P, Pacheco P, Lavinha J. 2000. Nonsense mutations in the human βglobin gene lead to unexpected levels of cytoplasmic mRNA accumulation. Blood 96: 2895-2901.
76. Rooks H., Clark B, Best S, Rushton P, Oakley M, Thein OS, Cuthbert A.C., Britland A, Ruf A, Thein SL. 2012. A novel 506 kb deletion causing 1γdβ thalassemia. Blood Cells Mol Dis 49: 121-127.
77. Rund D., Dowling C, Najjar K, Rachmilewitz EA, Kazazian HH Jr, Oppenheim A. 1992. Two mutations in the β-globin polyadenylylation signal reveal extended transcripts and new RNA polyadenylylation sites. Proc Natl Acad Sci 89: 4324-4328.
78. Rund D., Oron-Karni V, Filon D, Goldfarb A, Rachmilewitz E, Oppenheim A. 1997. Genetic analysis of β-thalassaemia intermedia in Israel: Diversity of mechanisms and unpredictability of phenotype. Am J Hematol 54: 16-22.
79. Saba L., Meloni A, Sardu R, Travi M, Primignani P, Rosatelli M.C., Cao A. 1992. A novel β-thalassemia mutation (G → A) at the initiation codon of the β-globin gene. Human Mutation 1: 420-422.
80. Safaya S., Rieder RF, Dowling CE, Kazazian HHJ, Adams JGI. 1989. Homozygous β-thalassemiawithout anemia. Blood 73: 324-328.
81. Schoenberg D.R., Maquat LE. 2012. Regulation of cytoplasmic mRNA decay. Nat Rev Genet 13: 246-259.
82. Schokker R.C., Went LN, Bok J. 1966. A newgenetic variant of β-thalassaemia. Nature 209: 44-46.
83. +thalassemic human globin gene. Proc Natl Acad Sci 78: 2455.
84. Stamatoyannopoulos G., Woodson R, Papayannopoulou T, Heywood D., Kurachi MS. 1974. Inclusion-body β-thalassemia trait. A form of β thalassemia producing clinical manifestation in simple heterozygotes. N Engl JMed 290: 939-943.
85. Swensen J.J., Agarwal AM, Esquilin JM, Swierczek S, Perumbeti A., Hussey D, Joiner CH, Pont-Kingdon G, Lyon E., Prchal JT. 2010. Sickle cell disease due to uniparental disomy in a child who inherited sickle cell trait. Blood 116: 2822-2825.
86. Takeshita K., Forget BG, Scarpa A, Benz EJ Jr. 1984. Intranuclear defect in β-globin mRNA accumulation due to a premature translation termination codon. Blood 64: 13-22.
87. Thein SL. 1998. β thalassaemia. In Baillière's clinical haematology, sickle cell disease and thalassaemia (ed. Rodgers GP), pp. 91-126. Baillière Tindall, London.
88. Thein SL. 1999. Is it dominantly inherited β thalassaemia or just a β-chain variant that is highly unstable? Br J Haematol 107: 12-21.
89. Thein SL. 2001. Structural Variants with a β-Thalassemia Phenotype. In Disorders of hemoglobin: Genetics, pathophysiology, and clinical management (ed. Steinberg MH, Forget B.G., Higgs DR, Nagel RL), pp. 342-355. Cambridge University Press, Cambridge, UK.
90. Thein SL. 2005. Pathophysiology of β thalassemia-A guide to molecular therapies. Hematology Am Soc Hematol Educ Program 31-37.
91. Thein S.L., Wood WG. 2009. The molecular basis of β thalassemia, dβ thalassemia, and hereditary persistence of fetal hemoglobin. In Disorders of hemoglobin: Genetics, pathophysiology, and clinical management (ed. Steinberg MH, Forget BG, Higgs DR, Nagel RL), pp. 323-356. Cambridge University Press, Cambridge, UK.
92. Thein S.L., Old JM, Wainscoat JS, Petrou M, Modell B, Weatherall DJ. 1984. Population and genetic studies suggest a single origin for the Indian deletion β0 thalassaemia. Br J Haematol 57: 271-278.
93. Thein S.L., Hesketh C, Taylor P, Temperley IJ, Hutchinson RM, Old JM, Wood WG, Clegg JB, Weatherall DJ. 1990. Molecular basis for dominantly inherited inclusion body β-thalassemia. Proc Natl Acad Sci 87: 3924-3928.
94. Thein S.L., Best S, Sharpe J, Paul B, Clark DJ, Brown MJ. 1991. Hemoglobin Chesterfield (β28 Leu → Arg) produces the phenotype of inclusion body β thalassemia. Blood 77: 2791-2793.
95. Thein S.L., Wood WG, Wickramasinghe SN, Galvin MC. 1993. β-Thalassemia unlinked to the β-globin gene in an English family. Blood 82: 961-967.
96. Traeger-Synodinos J, Tzetis M, Kanavakis E, Metaxotou-Mavromati A., Kattamis C. 1991. The Corfu dβ thalassaemia mutation in Greece: Haematological phenotype and prevalence. Br J Haematol 79: 302-305.
97. Treisman R., Orkin SH, Maniatis T. 1983. Specific transcription and RNA splicing defects in five cloned β-thalassaemia genes. Nature 302: 591-596.
98. Varawalla N.Y., Old JM, Weatherall DJ. 1991. Rare β-thalassaemia mutations in Asian Indians. Br J Haematol 79: 640-644.
99. Verhovsek M., Shah NR, Wilcox I, Koenig SC, Barros T, Thornburg C.D., Steinberg MH, Luo HY, Chui DH. 2012. Severe fetal and neonatal hemolytic anemia due to a 198 kb deletion removing the complete β-globin gene cluster. Pediatr Blood Cancer 59: 941-944.
100. Viprakasit V., Gibbons RJ, Broughton BC, Tolmie JL, Brown D., Lunt P, Winter RM, Marinoni S, Stefanini M, Brueton L., et al. 2001. Mutations in the general transcription factor TFIIH result in β-thalassaemia in individuals with trichothiodystrophy. Hum Mol Genet 10: 2797-2802.
101. Wainscoat J.S., Thein SL, WoodWG, Weatherall DJ, Tzotos S, Kanavakis E., Metaxatou-Mavromati A, Kattamis C. 1985. A novel deletion in the b globin gene complex. Ann NY Acad Sci 445: 20-27.
102. Wajcman H., Lahary A, Prome D, Kister J, Riou J, Godart C, Prehu C., Traeger-Synodinos J, Papassotiriou I, Galacteros F. 2001. Hb Mont Saint Aignan [β128(H6)Ala → Pro]: A new unstable variant leading to chronic microcytic anemia. Hemoglobin 25: 57-65.
103. Weatherall D.J., Clegg JB. 2001. The thalassaemia syndromes. Blackwell Science, Oxford.
104. Weatherall D.J., Clegg JB, Knox-Macaulay HHM, Bunch C, Hopkins C.R., Temperley IJ. 1973. A genetically determined disorder with features both of thalassaemia and congenital dyserythropoietic anaemia. Br J Haematol 24: 681-702.
105. +-thalassemia globin gene. Nucl Acid Res 9: 1777.
106. Wong C., Dowling CE, Saiki RK, Higuchi RG, Erlich HA, Kazazian HHJ. 1987. Characterization of β-thalassaemia mutations using direct genomic sequencing of amplified single copy DNA. Nature 330: 384-386.
107. Wong S.C., Stoning TA, Efremov GD, Huisman THJ. 1989. High frequencies of a rearrangement (+ATA; 2T) at 2530 to the β-globin gene in different populations indicate the absence of a correlation with a silent β-thalassemia determinant. Hemoglobin 13: 1-5.
108. Yang K.G., Kutlar F, George E, Wilson JB, Kutlar A, Stoming TA, Gonzalez-Redondo JM, Huisman THJ. 1989. Molecular characterization of β-globin gene mutations in Malay patients with Hb E-β-thalassaemia and thalassaemia major. Br J Haematol 72: 73-80.
109. Yu C., Niakan KK, Matsushita M, Stamatoyannopoulos G, Orkin S.H., Raskind WH. 2002. X-linked thrombocytopenia with thalassemia from a mutation in the amino finger of GATA-1 affecting DNA binding rather than FOG-1 interaction. Blood 100: 2040-2045.