Hemoglobinopathies in Southeast Asia: molecular biology and clinical medicine.

Thalassemia (thal) and hemoglobinopathies are widespread, recessive inherited diseases. Approximately 250 million people (4.5% of the world population) carry abnormal hemoglobin (Hb) genes. Southeast Asia consists of 10 countries, i.e. Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, the Philippines, Singapore, Thailand, and Vietnam, with a total population of more than 400 million. In most of these countries the population is ethnically heterogeneous. Thalassemias are common in Southeast Asia. α-Thalassemias are very prevalent, attaining frequencies of 20–40%. β-Thal, Hb Constant Spring (CS) and Hb E are also common, the latter attaining a frequency as high as 50–60% among certain populations (1). Abnormal genes in different combinations lead to more than 60 different thalassemic syndromes. The thalassemia disorders were originally confined to the tropics and subtropics. However, Southeast Asians are now scattered around the world and have carried with them most of the complex thalassemic conditions...

[1]  S. Fucharoen,et al.  Intracranial extramedullary hematopoiesis in β°‐thalassemia/hemoglobin E disease , 1981 .

[2]  D. Higgs,et al.  Characterization of two deletions that remove the entire human ζ‐α globin gene complex (—THAI and —FIL) , 1988 .

[3]  T. Sanguansermsri,et al.  Hemoglobin Suan-Dok (α2109(G16)LEU-ARGβ2). an Unstable Variant Associated with α-Thalassemia , 1979 .

[4]  A. Kutlar,et al.  Molecular characterization of β‐globin gene mutations in Malay patients with Hb E‐β‐thalassaemia and thalassaemia major , 1989 .

[5]  G. Wu,et al.  Studies of beta-thalassemia mutations in families living in three provinces in southern China. , 1989, Hemoglobin.

[6]  S. Fucharoen,et al.  A novel ochre mutation in the beta-thalassemia gene of a Thai. Identification by direct cloning of the entire beta-globin gene amplified using polymerase chain reactions. , 1989, The Journal of biological chemistry.

[7]  D. Weatherall,et al.  Concomitant inheritance of α‐thalassemia in β°‐thalassemia/hb e disease , 1985 .

[8]  S. Fucharoen,et al.  EF Bart's disease: Interaction of the abnormal α‐ and β‐globin genes , 1988 .

[9]  T Nakamura,et al.  One base substitution in IVS-2 causes a beta +-thalassemia phenotype in a Chinese patient. , 1984, Biochemical and biophysical research communications.

[10]  S. Fucharoen,et al.  Different molecular defects of Gγ (Aγδβ)°‐thalassaemia in Thailand , 1987 .

[11]  S. Fucharoen,et al.  Hemoglobinopathies in Southeast Asia. , 1987, Hemoglobin.

[12]  S. Thein.  DOMINANT β THALASSAEMIA: MOLECULAR BASIS AND PATHOPHYSIOLOGY , 1992 .

[13]  D. Weatherall,et al.  Characterization of the breakpoint of a 3.5-kb deletion of the β-globin gene , 1991 .

[14]  Y. Fukumaki,et al.  Eight-base deletion in exon 3 of the beta-globin gene produced a novel variant (beta khon kaen) with an inclusion body beta-thalassemia trait. , 1991, Blood.

[15]  A. Chaiprasert,et al.  Fatal arteritis due to Pythium insidiosum infection in patients with thalassaemia. , 1993, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[16]  P. Wasi.  Haemoglobinopathies including thalassaemia. Part 1: Tropical Asia. , 1981, Clinics in haematology.

[17]  S. Fucharoen,et al.  Detection of α‐thalassemia‐1 (Southeast Asian type) and its application for prenatal diagnosis , 1995 .

[18]  P. Winichagoon,et al.  Globin chain synthesis is heterozygous and homozygous hemoglobin E. , 1982, Hemoglobin.

[19]  The spectrum of β thalassaemia in Burma , 1992 .

[20]  D. Mager,et al.  A gene deletion ending within a complex array of repeated sequences 3' to the human beta-globin gene cluster. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[21]  P. Wilairat,et al.  Nondeletional type of hereditary persistence of fetal haemoglobin: molecular characterization of three unrelated Thai HPFH , 1994, British journal of haematology.

[22]  S. Fucharoen,et al.  Hemoglobin dhonburi α2β2 126 (H4) Val → Gly: A new unstable β variant producing a β‐thalassemia intermedia phenotype in association with β°‐Thalassemia , 1990 .

[23]  P. Wilairat,et al.  Severity differences in β‐thalassaemia/haemoglobin E syndromes: implication of genetic factors , 1993 .

[24]  Stylianos E. Antonarakis,et al.  Abnormal RNA processing due to the exon mutation of βE-globin gene , 1982, Nature.

[25]  S. Fucharoen,et al.  Thai Gγ(Aγ δβ)°-Thalassemia and its Interaction with a Single γ-GLOBIN Gene on a Chromosome Carrying β°-Thalassemia , 1990 .

[26]  J. Burnell,et al.  Relation between erythropoiesis and bone metabolism in thalassemia. , 1981, The New England journal of medicine.

[27]  T. Sanguansermsri,et al.  β -Thalassemia in A Thai Family Is Caused by A 3.4 Kb Deletion Including the Entire β-Globin Gene , 1990 .

[28]  P. Suwanagool,et al.  Distribution of pulmonary thromboembolic lesions in thalassemic patients. , 1987, Birth defects original article series.

[29]  P. Wilairat,et al.  Identification of five rare mutations including a novel frameshift mutation causing β0-thalassemia in Thai patients with β0-thalassemia/hemoglobin E disease , 1992 .

[30]  S. Fucharoen,et al.  HB Q-Thailand [α74(EF3)ASP→HIS] : gene organization, molecular structure, and DNA diagnosis , 1992 .

[31]  W. Wood,et al.  Instability of beta E-messenger RNA during erythroid cell maturation in hemoglobin E homozygotes. , 1982, The Journal of clinical investigation.

[32]  S. Issaragrisil,et al.  Spinal cord compression in thalassemia. Report of 12 cases and recommendations for treatment. , 1981, Archives of internal medicine.

[33]  Y. Fei,et al.  Types of thalassemia among patients attending a large university clinic in Kuala Lumpur, Malaysia. , 1992, Hemoglobin.

[34]  S. Fucharoen,et al.  Identification of Hb Lepore-Washington-Boston in association with Hb E [beta 26(B8)Glu----Lys] in a Thai female. , 1987, Hemoglobin.

[35]  S. Fucharoen,et al.  Severe infection in thalassemia: a prospective study. , 1987, Birth defects original article series.

[36]  S. Na-nakorn,et al.  Studies of the Distribution of Haemoglobin E, Thalassaemias and Glucose-6-phosphate Dehydrogenase Deficiency in North-eastern Thailand , 1967, Nature.

[37]  V. Fairbanks,et al.  Hematologic genetic disorders among Southeast Asian refugees , 1985, American journal of hematology.

[38]  A. Hill,et al.  Beta thalassemia in Melanesia: association with malaria and characterization of a common variant (IVS-1 nt 5 G----C). , 1988, Blood.

[39]  A. Hill,et al.  Independent recombination events between the duplicated human alpha globin genes; implications for their concerted evolution. , 1984, Nucleic acids research.

[40]  J. Clegg,et al.  Defective synthesis of HbE is due to reduced levels of βE mRNA , 1980, Nature.

[41]  S. Na-nakorn,et al.  Hereditary Persistence of Foetal Haemogloblll in a Thai Family: The First Instance in the Mongol Race and in Association with Haemoglobin E , 1968, British Journal of Haematology.

[42]  S. Fucharoen,et al.  β‐Thalassemia in Thailand a , 1990, Hemoglobin.

[43]  R. Trent,et al.  Thai (δβ)°-Thalassemia and its Lnteraction with γ-Thalassemia , 1988 .

[44]  Y. Fukumaki,et al.  Double heterozygosity of the β‐malay and a novel β‐thalassemia gene in a thai patient , 1991 .

[45]  S. Fucharoen,et al.  Hemoglobin constant spring in bangkok: Molecular screening by selective enzymatic amplification of the α2‐globin gene , 1991, American journal of hematology.

[46]  J. Clegg,et al.  Haemoglobin Constant Spring has an unstable α chain messenger RNA , 1982 .

[47]  M. Lim,et al.  Beta-thalassemia mutations in Indonesia and their linkage to beta haplotypes. , 1989, American journal of human genetics.

[48]  S. Fucharoen,et al.  The molecular basis of AE-Bart's disease. , 1989, Hemoglobin.

[49]  C. Baglioni.  The fusion of two peptide chains in hemoglobin Lepore and its interpretation as a genetic deletion. , 1962, Proceedings of the National Academy of Sciences of the United States of America.

[50]  R. W. Jones,et al.  (Aγδβ)° thalassaemia: similarity of phenotype in four different molecular defects, including one newly described , 1984, British journal of haematology.

[51]  M. Dalakas.  New neuromuscular symptoms after old polio ("the post-polio syndrome"): clinical studies and pathogenetic mechanisms. , 1987, Birth defects original article series.

[52]  S. Goodbourn,et al.  The molecular basis of alpha‐thalassaemia in Thailand. , 1984, The EMBO journal.

[53]  S. Fucharoen,et al.  Molecular basis of HbE-beta-thalassemia and the origin of HbE in northeast Thailand: identification of one novel mutation using amplified DNA from buffy coat specimens. , 1990, Biochemical and biophysical research communications.

[54]  D. Weatherall,et al.  The molecular basis of beta-thalassemia in Thailand: application to prenatal diagnosis. , 1990, American journal of human genetics.

[55]  S. Fucharoen,et al.  Determination for different severity of anemia in thalassemia: concordance and discordance among sib pairs. , 1984, American journal of medical genetics.

[56]  J. D. Etlinger,et al.  ATP-dependent proteolysis in red blood cell precursors. , 1987, Birth defects original article series.

[57]  P. Wasi.  LEVELS OF HAEMOGLOBIN H AND PROPORTIONS OF RED CELLS WITH INCLUSION BODIES IN THE TWO TYPES OF HAEMOGLOBIN H DISEASE , 1980, British journal of haematology.

[58]  T. Huisman,et al.  Homozygosity for a New Type of Gγ(Aγδβ)°-Thalassemia in a Malaysian Male , 1986 .