Southeast Asian Ovalocytosis (SAO) is a common red blood cell disorder that is maintained as a balanced polymorphism in human populations. In individuals heterozygous for the SAO-causing mutation there are minimal detrimental effects and well-documented protection from severe malaria caused by Plasmodium vivax and Plasmodium falciparum; however, the SAO-causing mutation is fully lethal in utero when homozygous. The present-day high frequency of SAO in Island Southeast Asia indicates the trait is maintained by strong heterozygote advantage. Our study elucidates the evolutionary origin of SAO by characterizing DNA sequence variation in a 9.5 kilobase region surrounding the causal mutation in the SLC4A1 gene. We find substantial haplotype diversity among SAO chromosomes and estimate the age of the trait to be approximately 10,005 years (95% CI: 4930-23,200 years). This date is far older than any other human malaria-resistance trait examined previously in Southeast Asia, and considerably pre-dates the widespread adoption of agriculture associated with the spread of speakers of Austronesian languages some 4000 years ago. Using a genealogy-based method we find no evidence of historical positive selection acting on SAO (s=0.0, 95% CI: 0.0-0.03), in sharp contrast to the strong present-day selection coefficient (e.g., 0.09) estimated from the frequency of this recessively lethal trait. This discrepancy may be due to a recent increase in malaria-driven selection pressure following the spread of agriculture, with SAO targeted as a standing variant by positive selection in malarial populations.

Two hundred and twenty-five G6PD-deficient subjects in Songklanagarind Hospital in the south of Thailand comprising 210 males and 15 females were studied. Neonatal jaundice was detected in 85% of these patients. Acute hemolysis related to infection was detected in 17.3% of the G6PD-deficient subjects. Drug-induced acute hemolysis was detected in 1.8% and favism was observed in 3.6% of G6PD-deficient patients. The molecular analysis was performed on 134 G6PD-deficient individuals by a combination of PCR-RFLP, multiplex polymerase chain reaction by multiple tandem forward primers and a common reverse primer assay (MPTP) and DNA sequencing to characterize the mutations of the samples with abnormal MPTP bands. We found 10 different missense G6PD mutations and the three most common variants were G6PD Viangchan 871,G→A (31.3%), G6PD Kaiping 1388,G→A (20.1%) and G6PD Mahidol 487,G→A (17.2%) followed by G6PD Canton 1376,G→T (9.7%), G6PD Union 1360,C→T (2.2%), G6PD Gaohe 95,A→G (1.5%), G6PD Quing Yuan 392,G→T (0.7%), G6PD Mediterranean 563,C→T (0.7%), G6PD Songklanagarind 196,T→A (0.7%), silent mutation 1311,C→T (6.7%), and uncharacterized variant (9%). A novel missense mutation at codon 196, TTC→ATC in exon 4 of the G6PD gene predicting a single amino acid substitution, Phe66Ile was identified and we designated this novel class II variant as G6PD Songklanagarind. The G6PD variants among the Thais in the southern part are heterogeneous and G6PD Viangchan, Kaiping, Mahidol, and Canton variants account for about 78% of the cases. Our findings provide some evidence that G6PD Viangchan and Mahidol are common Southeast Asian variants and support the theory of genetic drifts throughout Southeast Asia.

Growth patterns of 85 survivors of childhood leukemia were analyzed retrospectively. All patients remained in first remission with no central nervous system involvement. The mean age at diagnosis was 5.8 +/- 3.6 years. The diagnoses were acute lymphoblastic leukemia (ALL) in 68 patients (80%) and acute non-lymphoblastic leukemia (ANLL) in 17 patients (20%). All except two patients received cranial irradiation: 51 patients with 1,800 cGy and 32 patients with 2,400 cGy. Mean height SDS was -0.7 +/- 1.36 at the time of diagnosis, which decreased to -0.92 +/- 1.31 by the end of treatment, and further decreased to -1.14 +/- 1.38 at 6 years after cessation of treatment. Mean weight SDS was -0.55 +/- 1.13 at the time of diagnosis, increasing slightly to -0.39 +/- 1.02 at the end of treatment, and decreasing to -0.46 +/- 1.65 at 6 years after cessation of treatment. Of these survivors, 51 patients (26 boys and 25 girls) reached a final height that was 1.04 SDS or 5.3 cm less than their target height. There was no difference of height and weight SDS between patients with ALL and ANLL. Girls and boys had different growth patterns. Girls had a slightly increased height SDS and gained more weight after cessation of treatment, resulting in less final height deficit and overweight for height, whereas boys had further height and weight reduction resulting in more deficit of final height.

Medical and Pediatric OncologyVolume 40, Issue 1 p. 51-53 Brief ReportFree Access True histiocytic lymphoma following acute lymphoblastic leukemia Malai Wongchanchailert MD, Corresponding Author Malai Wongchanchailert MD [email protected] Department of Pediatrics, Faculty of Medicine, Prince of Songkhla University, Hat Yai, Songkhla, ThailandDepartment of Pediatrics, Faculty of Medicine, Prince of Songkhla University, Hat Yai, Songkhla, Thailand. 90110.Search for more papers by this authorVichai Laosombat MD, Vichai Laosombat MD Department of Pediatrics, Faculty of Medicine, Prince of Songkhla University, Hat Yai, Songkhla, ThailandSearch for more papers by this author Malai Wongchanchailert MD, Corresponding Author Malai Wongchanchailert MD [email protected] Department of Pediatrics, Faculty of Medicine, Prince of Songkhla University, Hat Yai, Songkhla, ThailandDepartment of Pediatrics, Faculty of Medicine, Prince of Songkhla University, Hat Yai, Songkhla, Thailand. 90110.Search for more papers by this authorVichai Laosombat MD, Vichai Laosombat MD Department of Pediatrics, Faculty of Medicine, Prince of Songkhla University, Hat Yai, Songkhla, ThailandSearch for more papers by this author First published: 07 November 2002 https://doi.org/10.1002/mpo.10056Citations: 5AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. REFERENCES 1 Cline MJ. Histiocytes and histiocytosis. Blood 1994; 84: 2840– 2853. 2 Bucsky P, Favara B, Feller AC, et al. Malignant histiocytosis and large cell anaplastic (Ki-1) lymphoma in childhood: guidelines for differential diagnosis-report of the Histiocyte Society. Med Pediatr Oncol 1994; 22: 200– 203. 3 Egeler RM, Schmitz L, Sonneveld P, et al. Malignant histiocytosis: a reassessment of cases formerly classified as histiocytic neoplasms and review of the literature. Med Pediatr Oncol 1995; 25: 1– 7. 4 Levine EG, Hanson CA, Jaszcz W, et al. True histiocytic lymphoma. Semin Oncol 1991; 18: 39– 49. 5 Lukes RJ, Parker JW, Taylor CR, et al. Immunologic approach to non-Hodgkin's lymphoma and related leukemias. Analysis of the results of multiparameter studies of 425 cases. Semin Haematol 1978; 15: 322– 351. 6 Hanson CA, Jaszcz W, Kersey JH, et al. True histiocytic lymphoma: histopathologic, immunophenotypic and genotypic analysis. Br J Haematol 1989; 73: 187– 198. 7 Ralfkiaer E, Delsol G, O'Connor NTJ, et al. Malignant lymphomas of true histiocytic origin. A clinical, histological, immunophenotypic and genotypic study. J Pathol 1990; 160: 9– 17. 8 Soria C, Orradre JL, Garcia-Almagro D, et al. True histiocytic lymphoma (monocytic sarcoma). Am J Dermatopathol 1992; 14: 511– 517. 9 Mirchandani L, Shah I, Palutke M, et al. True histiocytic lymphoma. A report of four cases. Cancer 1983; 52: 1911– 1918. 10 Hsu SM, Ho YS, Hsu PL. Lymphomas of true histiocytic origin. Expression of different phenotypes in so-called true histiocytic lymphoma and malignant histiocytosis. Am J Pathol 1991; 138: 1389– 1404. 11 Milchgrub S, Kamel OW, Wiley E, et al. Malignant histiocytic neoplasms of the small intestine. Am J Surg Pathol 1992; 16: 11– 20. 12 Copie-Bergman C, Wotherspoon AC, Norton AJ, et al. True histiocytic lymphoma. A morphologic, immunohistochemical, and molecular genetic study of 13 cases. Am J Surg Pathol 1998; 22: 1386– 1392. 13 Soslow RA, Davis RE, Warnke RA, et al. True histiocytic lymphoma following therapy for lymphoblastic neoplasms. Blood 1996; 87: 5207– 5212. 14 Knapp W, Rieber P, Dorken B, et al. Towards a better definition of human leucocyte surface molecules. Immunol Today 1989; 10: 253– 258. 15 Miettinen M, Fletcher CDM, Lasota J. True histiocytic lymphoma of small intestine. Analysis of two S-100 protein-positive cases with features of interdigitating reticulum cell sarcoma. Am J Clin Pathol 1993; 100: 285– 292. 16 Karcher DS, Head DR, Mullins JD. Malignant histiocytosis occurring in patients with acute lymphoblastic leukemia. Cancer 1978; 41: 1967– 1973. 17 Skoog DP, Feagler JR. T cell acute lymphoblastic leukemia terminating as malignant histiocytosis. Am J Med 1978; 64: 678– 682. 18 Trubowitz S, Sobel H, David S. Null cell (non-T, non-B) acute lymphoblastic leukemia terminating as malignant histiocytosis. Am J Clin Pathol 1980; 73: 725– 730. 19 Starkie CM, Kenny MW, Mann JR, et al. Histiocytic medullary reticulosis following acute lymphoblastic leukemia. Cancer 1981; 47: 537– 544. 20 Yin JAL, Kumaran TO, Marsh GW, et al. Complete recovery of histiocytic medullary reticulosis-like syndrome in a child with acute lymphoblastic leukemia. Cancer 1983; 51: 200– 202. 21 Liang D, Chu ML, Shih C. Reactive histiocytosis in acute lymphoblastic leukemia and non Hodgkin's lymphoma. Cancer 1986; 58: 1289– 1294. 22 Takasaki N, Kaneko Y, Maseki N, et al. Hemophagocytic syndrome complicating T-cell acute lymphoblastic leukemia with a novel t (11;14) (p15; q11) chromosome translocation. Cancer 1987; 59: 424– 428. 23 Elghetany MT. True histiocytic lymphoma: Is it an entity? Leukemia 1997; 11: 762– 764. Citing Literature Volume40, Issue1January 2003Pages 51-53 ReferencesRelatedInformation

Medical and Pediatric OncologyVolume 38, Issue 4 p. 266-268 International Note The treatment of children with acute lymphoblastic leukemia in Thailand Vichai Laosombat MD, MSc (Pediatr), Corresponding Author Vichai Laosombat MD, MSc (Pediatr) lvichai@ratree.psu.ac.th Department of Pediatrics, Division of Pediatric Hematology and Oncology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, ThailandDepartment of Pediatrics, Faculty of Medicine, Division of Pediatric Hematology and Oncology, Prince of Songkla University, Hat Yai, Songkla 90110, Thailand.Search for more papers by this authorMalai Wongchanchailert MD, Malai Wongchanchailert MD Department of Pediatrics, Division of Pediatric Hematology and Oncology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, ThailandSearch for more papers by this authorBenjamas Sattayasevana MSc, Benjamas Sattayasevana MSc Department of Pediatrics, Division of Pediatric Hematology and Oncology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, ThailandSearch for more papers by this authorAranya Wiriyasateinkul BSc, Aranya Wiriyasateinkul BSc Department of Pediatrics, Division of Pediatric Hematology and Oncology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, ThailandSearch for more papers by this authorSomchai Watana-Arepornchai MD, Somchai Watana-Arepornchai MD Department of Radiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, ThailandSearch for more papers by this author Vichai Laosombat MD, MSc (Pediatr), Corresponding Author Vichai Laosombat MD, MSc (Pediatr) lvichai@ratree.psu.ac.th Department of Pediatrics, Division of Pediatric Hematology and Oncology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, ThailandDepartment of Pediatrics, Faculty of Medicine, Division of Pediatric Hematology and Oncology, Prince of Songkla University, Hat Yai, Songkla 90110, Thailand.Search for more papers by this authorMalai Wongchanchailert MD, Malai Wongchanchailert MD Department of Pediatrics, Division of Pediatric Hematology and Oncology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, ThailandSearch for more papers by this authorBenjamas Sattayasevana MSc, Benjamas Sattayasevana MSc Department of Pediatrics, Division of Pediatric Hematology and Oncology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, ThailandSearch for more papers by this authorAranya Wiriyasateinkul BSc, Aranya Wiriyasateinkul BSc Department of Pediatrics, Division of Pediatric Hematology and Oncology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, ThailandSearch for more papers by this authorSomchai Watana-Arepornchai MD, Somchai Watana-Arepornchai MD Department of Radiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, ThailandSearch for more papers by this author First published: 12 March 2002 https://doi.org/10.1002/mpo.1321Citations: 8AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume38, Issue4April 2002Pages 266-268 RelatedInformation

We report a Thai family in which five members are Hb G-Makassar heterozygotes and one member is, in addition, a heterozygote for beta(0)-thalassemia (IVS-I-1, G --> T). We confirm that the previously presumed mutation at codon 6 of the beta-globin gene is GAG --> GCG. Hb G-Makassar heterozygotes are asymptomatic and hematologically normal. The Hb G-Makassar/beta(0)-thalassemia compound heterozygote has features of thalassemia minor. A simple and rapid polymerase chain reaction-restriction fragment length polymorphism for the detection of Hb G-Makassar is described.

BACKGROUND:Gilbert's syndrome is a common inherited disorder of bilirubin metabolism contributing to the development of neonatal jaundice and causing recurrent jaundice after the neonatal period. In the patients with Gilbert's syndrome, mutations have been reported in the promoter and exons of the uridine diphosphate-glucuronosyl transferase 1 (UGT1A1) gene on chromsome 2q37, which encodes bilirubin uridine diphosphate-glucuronosyltransferase. However, the genetic basis of Gilbert's syndrome, including its inheritance trait, remains to be clarified.METHODS:Patients 1 and 2 were Thai sisters with Gilbert's syndrome. They had a history of prolonged neonatal jaundice and showed recurrent jaundice after their infancy, while the parents showed no symptoms. To search for the mutation in the patients, all exons of the UGT1A1 gene were amplified by polymerase chain reaction (PCR) and sequenced directly. The frequency of the mutation in controls was studied by PCR-restriction enzyme digestion method.RESULTS:The patients were homozygous for a novel single transition of T to C at nucleotide position 247 (exon 1), which would predict a substitution of leucine for phenylalanine at codon 83 of the enzyme protein. No other mutation was detected in any regions except exon 1. The parents with no symptoms showed heterozygosity for the mutation. Among the 110 Japanese controls, no homozygous individuals and three heterozygous individuals for the mutation were identified, giving a mutated allele frequency of 0.0136.CONCLUSIONS:A novel missense mutation in the UGT1A1 gene was identified in two Thai siblings with Gilbert's syndrome. The affected family showed that homozygosity for the mutation may lead to apparent symptoms and that the syndrome was inherited as an autosomal recessive trait. The mutation does not explain a high incidence of neonatal jaundice in Japan, because it is very rare in the Japanese population.

BACKGROUND AND OBJECTIVES Frameshift 41/42 mutation is the most common mutation of beta0-thalassemia found in Thailand. We studied clinical and hematologic features in 84 patients and relatives with frameshift 41/42 to determine whether it is possible to predict phenotypic severity from genetic factors. DESIGN AND METHODS The clinical phenotypes and hematologic data of Thai patients with frameshift 41/42 were studied. Alpha-thalassemia, Hb Constant Spring (HbCS) genes and the presence of Xmnl-Ggamma polymorphism were studied in patients who had mild symptoms. RESULTS Homozygotes for frameshift 41/42 and compound heterozygotes for frameshift 41/42 and beta0-thalassemia produced severe symptoms and have a thalassemia major phenotype. Combination of frameshift 41/42 and beta0-thalassemia or Hb E produced mild to moderate symptoms with thalassemia intermedia phenotype and severe symptoms with thalassemia major phenotype. The co-inheritance of beta-thalassemia or HbCS gene or the presence of Xmnl-Ggamma polymorphism was not associated with mild disease in patients with frameshift 41/42 and HbE. INTERPRETATION AND CONCLUSIONS The clinical phenotype of homozygotes for frameshift 41/42 and compound heterozygotes for frameshift 41/42 and beta0-thalassemia could be used to predict a severe phenotype with thalassemia major. However, the clinical phenotype of compound heterozygotes of frameshift 41/42 and beta0-thalassemia or Hb E were variable and could not be accurately predicted. Associations between concomitant alpha-thalassemia or HbCS of the presence of Xmnl-Ggamma polymorphism and a mild clinical phenotype are not apparent, indicating the involvement of other ameliorating determinants or genetic modifications.

Seventy-eight patients with IVS-1 nt 5, G-C, which is the common mutation of beta (+)-thalassemia found in the southern part of Thailand, were studied to determine whether it is possible to predict phenotypic severity from genetic factors. The clinical phenotype of homozygotes for IVS-1 nt 5, G-C and compound heterozygotes for IVS-1 nt 5, G-C and beta degrees - or beta (+)-thalassemia were variable and could not be accurately predicted. The associations between concomittant alpha -thalassemia or Hb CS or the presence of XmnI-(G)gamma polymorphism and a mild clinical phenotype are not apparent, indicating the involvement of other ameliorating determinants or genetic modifications.

Forty-one patients with codon 17, A-T mutation of beta-thalassemia, which is commonly found in Thailand, were studied to determine whether it is possible to predict phenotypic severity from genetic factors. The clinical phenotype of homozygotes for codon 17, A-T and compound heterozygotes for codon 17, A-T and beta+-thalassemia may be used to predict a severe phenotype with TM. However, the clinical phenotype of compound heterozygotes for codon 17, A-T and beta+-thalassemia or Hb E were variable and could not be accurately predicted. The association of alpha-thalassemia2 and milder disease was and was not evident in patients with codon 17, A-T and Hb E. The association between Hb CS gene or the presence of XmnI-Ggamma polymorphism and a mild clinical phenotype is not apparent, indicating the involvement of other ameliorating determinants or genetic modifications.

One hundred and sixty-eight children aged 13 months to 12.6 years with acquired platelet dysfunction with eosinophilia (APDE) were studied. The male to female ratio was 1.15:1. All of the children were in good health and no history of any drug ingestion was detected. All of the children had widespread spontaneous bruising on the extremities, body and face off and on. Severe bleeding symptoms were detected in 8% of these patients. The number of platelets in these children was within the normal range but the platelet morphology was abnormal in all of them. Eosinophilia was detected in 86% of these children. Prolonged bleeding time was detected in 53% of these patients. Abnormal platelet adhesiveness was found in 33% of cases. Abnormal platelet aggregation induced by collagen was the most sensitive test in these patients. Abnormal ADP release from the platelets was detected in these patients by the absence of a second wave of aggregation during stimulation of PRP by ADP or epinephrine. Abnormal or no ATP secretion from the platelets during stimulation by ADP, epinephrine or collagen was detected in these patients. Ristocetin-induced platelet aggregation was normal in these children. Decreased or absence of platelet dense granules by TEM study was detected in some patients. These changes in platelet functions and morphology may be due to acquired storage pool deficiency of the platelet. Parasitic infection was detected in 56% of these children. About 83% of these children with APDE had serum total IgE higher than 100 IU/ml. There was no correlation between the number of eosinophils and serum total IgE and the severity of bleeding symptoms. The majority of children with APDE did not receive any treatment except those who had severe bleeding symptoms which required platelet concentrate to stop bleeding. In more than 90% of the patients, the bruising or ecchymosis disappeared within 6 months and the abnormal platelet functions returned to normal within 4 months. Recurrence of these bleeding syndromes was detected in 7% of the children.

We report a Thai boy with a compound heterozygosity for the α2 polyadenylation signal mutation (AATAAA → AATA– –) and α0-thalassemia (– –SEA), who suffered from Hb H disease with more severe clinical symptoms than those usually observed with deletional Hb H disease. His Hb H level was as high as 52% of total hemoglobin. The hematologic data of this unusual case of Hb H disease was compared with those of Hb H disease with a homozygosity for the α2 polyadenylation signal mutation, and compound heterozygosity of the α2 polyadenylation signal mutation and α0-thalassemia. A simple DNA assay based on an allele specific polymerase chain reaction for the detection of this polyadenylation signal mutation is described.

A prospective and descriptive study was carried out in 17 children with chronic ITP. Five-day course of Intraglobin (400 mg/kg/d x 5) was given intravenously to 10 children with the age of 4-16 years (5 males and 5 females). Two-day course of Venoglobulin-I (1 g/kg/d x 2) was given intravenously to 7 children with the age of 3-15 years (3 males and 4 females). Intraglobin and Venoglobulin-I were effective in treating children with chronic ITP. All of the patients had transient increased in their platelet counts during the first 2 weeks. The two-day course of Venoglobulin-I was superior to the five-day course of Intraglobin. Mild adverse effects were observed in a greater percentage of patients treated by Venoglobulin-I than in patients treated by Intraglobin. Intravenous immunoglobulin was one of the choices of treatment in children with chronic ITP, but the cost of immunoglobulin or gamma globulin is quiet high.

Abstract: The molecular defects of the factor XIII A subunit gene were studied in a patient with factor XIII deficiency. Mutation analysis was performed on amplified DNA from each exon of this gene by single‐strand conformation polymorphism (SSCP) and DNA sequencing techniques. A substitution of guanine by adenine at nucleotide 1258 in exon 10 of the coagulation factor XIII A subunit gene has been identified in the patient. The mutation results in the replacement of Gly420 by Ser in the core domain of the enzyme. Restriction enzyme analysis of amplified exon 10 DNA confirmed that the patient was homozygous for this mutation. A family study revealed that the mutation was inherited from both parents, who were first cousins. The potential effects of the mutation were predicted by molecular modeling of the amino acid substitution within the coordinates of the crystal structure. The substitution occurred within the core domain of the enzyme at a residue completely conserved among all known members of the transglutamin‐ase family. The model of the mutant protein suggests that although the substitution of Gly420 by Ser causes only minor readjustment of the residues and does not appear to be particularly deleterious in terms of structure, the mutation is, however, likely to decrease the molecule's ability to undergo the conformational change that is thought to be required for full transglutaminase activity. Our data strongly support the previously published information about the functional significance of the residues surrounding, but not forming, the catalytic pocket in the A subunit of factor XIII.

We report, herein, an infant who is twin A of a dizygotic twin, with premature birth and both twins having hemoglobin (Hb) E heterozygosity. Twin A who had Southeast Asian ovalocytosis (SAO) developed neonatal jaundice at the age of 2 days and needed phototherapy at the age of 3 days. The microbilirubin level was rapidly rising up to 535.2 μmol/L (31.3 mg/dl) with the hematocrit value of 38% at the age of 4 days prior to exchange blood transfusion. Exchange blood transfusion was done by 220 ml of O, Rh positive packed red blood cell reconstituted with 180 ml of O, Rh positive fresh plasma to lower the bilirubin level. Twin A received phototherapy from about 8 hr prior to exchange blood transfusion until 3 days later. Twin B, who did not have SAO, developed neonatal hyperbilirubinemia and needed only phototherapy. Twin A received a deletion of 27 basepairs in the erythroid band 3 gene and Hb E heterozygosity from his father. Am. J. Hematol. 60:136–139, 1999. © 1999 Wiley-Liss, Inc.

A total of 50 patients and relatives were studied comprising 12 cases of compound heterozygosity of beta-Malay and beta + thalassemia, 10 cases of compound heterozygosity of beta-Malay and beta degree thalassemia, 10 cases of beta-Malay and HbE and 18 cases of beta-Malay heterozygosity. Patients with beta-Malay and HbE had very mild clinical symptoms or were asymptomatic of thalassemia disease in the absence of blood transfusion. Homozygosity of beta-Malay produce mild clinical symptoms of thalassemic disease with normal facial characteristics and were not transfusion dependent. Patients with beta-Malay and IVS 1 nt 5 (G-C) had severe clinical symptoms, and were transfusion dependent. Patients with beta-Malay and beta degree thalassemia had severe clinical symptoms, delayed weight and height in relation to age, were transfusion dependent and had classical features of thalassemic diseases.

beta-Thalassemia mutations in 221 chromosomes of unrelated southern Thai patients were analyzed. Using dot blot hybridization of PCR amplified DNA with 15 allele specific oligonucleotide probes for beta-thalassemia mutations 196/221 (89%) of the alleles were characterized. Ten mutations were identified, of which six [codon 41/42 (TTCTTT-TT), IVS1 nt5(G-C), codon 19 (AAC-AGC), codon 17 (AAG-TAG), IVS1 nt1(G-T), -28 TATA (A-G)], accounted for 85%. Among the 25 uncharacterized alleles, 15 were analyzed by automated fluorescent DNA sequencing of the whole beta-globin gene with normal results in 7 alleles. Four mutations, previously described were detected in 8 alleles. They were a G-A at IVS1 nt1 in one heterozygote, a G-T at IVS1 nt1 in one heterozygote, codon 15 (TGG-TAG) in two heterozygotes and poly A(AATAAA-AATAGA) in two homozygotes. The polyadenylation mutations, previously demonstrated in the Malaysian population have been first detected in Thailand. It is remarkable that the IVS1 nt1 (G-A) mutation, previously reported in the Mediterranean population has been found only in the south of Thailand. This mutation was probably imported from Portugal. In former times the Portuguese had settled in Phuket in southern Thailand. In order to find a causative mutation in the rest of 7 true unknowns we performed direct DNA sequencing of the core fragments of the beta-Locus Control Region Hypersensitive Sites (LCR HS) 2,3 and 4 in these 7 samples. DNA sequencing of HS2 and HS3 fragments showed normal results. The heterozygote A/G was present in the palindromic sequence of the LCR HS4 (TGGGGACCCCA) in 6 beta-thalassemia samples. The same heterozygote A/G was found in 5/12 normal subjects. The allele frequency of A (0.79) is obviously higher than that of G (0.21). This could be due to the stability of the palindromic structure. When an A is in the middle of the palindromic sequence, the hairpin structure is formed. In contrast the hairpin structure disappears when a G is in the middle of the palindromic sequence. This structure is not further symmetric and may not be so stable as the hairpin structure. beta-Thalassemia mutations in southern Thailand are very heterogeneous and their distribution is different from other parts of the country.

Among a sample of 29 unrelated Thai Muslim children, a total of 37 beta thalassemia genes was identified and 33 out of 37 mutations (89%) were characterized giving 6 different mutations. Four mutations [IVS-1 nt 5 (G-C), codon 19 (A-G), codons 41/42 (-CTTT) and IVS-1 nt 1 (G-T)] account for 86%. IVS-1 nt 5 (G-C) is the most common mutation found in Thai Muslim patients. Thai Muslim patients share the four most common mutations with Malays.

One hundred and one thalassemic patients, 37 with homozygous beta-thalassemia, 60 with beta-thalassemia Hb E and 4 with hemoglobin H disease with Hb Constant Spring were studied. Twenty-four of 101 (23.8%) tested positive for antibody to hepatitis C virus (anti-HCV). Anti-HCV positivity among those with homozygous beta-thalassemia was significantly higher than anti-HCV positivity among the beta-thalassemic Hb E group. The number of blood transfusions received by anti-HCV positive thalassemic patients was significantly higher than that by anti-HCV negative thalassemic patients. Ninety per cent of anti-HCV positive thalassemic patients had persistently or intermittently raised SGPT levels.