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  1. Fulltext The use of the amplification refractory mutation system (arms) in the detection of rare beta-thalassemia mutations in the Malays and Chinese in Malaysia
    Chan YF, Tan KL, Wong YC, Wee YC, Yap SF, Tan JAMA
    Southeast Asian J. Trop. Med. Public Health, 2001 Dec;32(4):872-9.
    PMID: 12041567
    Molecular characterization and prenatal diagnosis for beta-thalassemia can be carried out using the Amplification Refractory Mutation System (ARMS). The ARMS is a rapid and direct molecular technique in which beta-thalassemia mutations are visualized immediately after DNA amplification by gel electrophoresis. In the University of Malaya Medical Center, molecular characterization and prenatal diagnosis for beta-thalassemia is carried out using ARMS for about 96% of the Chinese and 84.6% of the Malay patients. The remaining 4% and 15.4% of the uncharacterized mutations in the Chinese and Malay patients respectively are detected using DNA sequencing. DNA sequencing is an accurate technique but it is more time-consuming and expensive compared with the ARMS. The ARMS for the rare Chinese beta-mutations at position -29 (A-->G) and the ATG-->AGG base substitution at the initiator codon for translation in the beta-gene was developed. In the Malays, ARMS was optimized for the beta-mutations at codon 8/9 (+G), Cap (+1) (A-->C) and the AATAAA-->AATAGA base substitution in the polyadenylation region of the beta-gene. The ARMS protocols were developed by optimization of the parameters for DNA amplification to ensure sensitivity, specificity and reproducibility. ARMS primers (sequences and concentration), magnesium chloride concentration, Taq DNA polymerase and PCR cycling parameters were optimized for the specific amplification of each rare beta-thalassemia mutation. The newly-developed ARMS for the 5 rare beta-thalassemia mutations in the Chinese and Malays in Malaysia will allow for more rapid and cost-effective molecular characterization and prenatal diagnosis for beta-thalassemia in Malaysia.
    Matched MeSH terms: beta-Thalassemia/diagnosis
  2. Fulltext Spectrum of beta-thalassaemia mutations in transfusion dependent thalassaemia patients: practical implications in prenatal diagnosis
    George E, George R, Ariffin WA, Mokhtar AB, Azman ZA, Sivagengei K
    Med J Malaysia, 1993 Sep;48(3):325-9.
    PMID: 8183146
    The study concerned the identification of the beta-thalassaemia mutations that were present in 24 patients with beta-thalassaemia major who were transfusion dependent. The application of a modified polymerase chain reaction, the amplification refractory system (ARMS) was found to be an effective and rapid method for the identification of the beta-thalassaemia mutations. Six different mutations were detected. Seventy five percent of the patients were Chinese-Malaysians and showed the commonly occurring anomalies: 1. frameshift codon 41 and 42 (-TCTT); 2. the C to T substitution at position 654 of intron 2 (IVS-2); 3. the mutation at position -28(A to G); and the nonsense mutation A to T at codon 17. In the Malays, the common mutations seen were: 1. the G to C mutation at position 5 of IVS-1; 2. the G to T mutation at position 1 of intron 1 (IVS-1); and the A to T at codon 17. The delineation of the specific mutations present will enable effective prenatal diagnosis for beta-thalassaemia to be instituted.
    Matched MeSH terms: beta-Thalassemia/diagnosis
  3. Fulltext First trimester prenatal diagnosis of beta-thalassaemia following chorionic villus sampling
    Chandran R, Ainoon O, Anson I, Anne J, Cheong SK
    Med J Malaysia, 1993 Sep;48(3):341-4.
    PMID: 8183149
    DNA analysis for the diagnosis of beta-thalassaemia is a relatively new technique in Malaysia. This, combined with chorionic villus sampling, has enabled us to offer prenatal diagnosis in the first trimester for this common condition. To the best of our knowledge, this has not hitherto been reported in Malaysia.
    Matched MeSH terms: beta-Thalassemia/diagnosis*
  4. Chronic haemolytic anaemia; a report of three cases of Cooley's anaemia and five cases of acholuric jaundice seen in Malaya with a discussion on the differential diagnosis
    FIELD CE, TAN EE
    Med J Malaya, 1955 Sep;10(1):60-82.
    PMID: 13287496
    Matched MeSH terms: beta-Thalassemia/diagnosis*
  5. Fulltext Co-inheritance of compound heterozygous Hb Constant Spring and a single -alpha(3.7) gene deletion with heterozygous deltabeta thalassaemia: a diagnostic challenge
    Azma RZ, Othman A, Azman N, Alauddin H, Ithnin A, Yusof N, et al.
    Malays J Pathol, 2012 Jun;34(1):57-62.
    PMID: 22870600
    Haemoglobin Constant Spring (Hb CS) mutation and single gene deletions are common underlying genetic abnormalities for alpha thalassaemias. Co-inheritance of deletional and non-deletional alpha (alpha) thalassaemias may result in various thalassaemia syndromes. Concomitant co-inheritance with beta (beta) and delta (delta) gene abnormalities would result in improved clinical phenotype. We report here a 33-year-old male patient who was admitted with dengue haemorrhagic fever, with a background history of Grave's disease, incidentally noted to have mild hypochromic microcytic red cell indices. Physical examination revealed no thalassaemic features or hepatosplenomegaly. His full blood picture showed hypochromic microcytic red cells with normal haemoglobin (Hb) level. Quantitation of Hb using high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) revealed raised Hb F, normal Hb A2 and Hb A levels. There was also small peak of Hb CS noted in CE. H inclusions was negative. Kleihauer test was positive with heterocellular distribution of Hb F among the red cells. DNA analysis for alpha globin gene mutations showed a single -alpha(-3.7) deletion and Hb CS mutation. These findings were suggestive of compound heterozygosity of Hb CS and a single -alpha(-3.7) deletion with a concomitant heterozygous deltabeta thalassaemia. Co-inheritance of Hb CS and a single -alpha(-3.7) deletion is expected to result at the very least in a clinical phenotype similar to that of two alpha genes deletion. However we demonstrate here a phenotypic modification of alpha thalassemia presumptively as a result of co-inheritance with deltabeta chain abnormality as suggested by the high Hb F level.
    Matched MeSH terms: beta-Thalassemia/diagnosis*
  6. HbA2 levels in normal, beta-thalassaemia and haemoglobin E carriers by capillary electrophoresis
    Hafiza A, Malisa MY, Khirotdin RD, Azlin I, Azma Z, Thong MC, et al.
    Malays J Pathol, 2012 Dec;34(2):161-4.
    PMID: 23424780
    The capillary electrophoresis (CE) is a new system that utilizes the principle of electrokinetic separation of molecules in eight electrolyte buffer-filled silica capillaries. In this study, we established the normal ranges of haemoglobin A2 (HbA2) and haemoglobin F (HbF) levels for normal individuals using this system and also the HbA2 level in beta thalassaemia and haemoglobin E (HbE) individuals.
    Matched MeSH terms: beta-Thalassemia/diagnosis
  7. Microcytic to hypochromic ratio as a discriminant index of thalassaemia trait in subjects with hypochromic anaemia
    Wee SY, Muhamed Said SS, Raja Sabudin RZA, Alauddin H, Ithnin A
    Malays J Pathol, 2020 Aug;42(2):195-201.
    PMID: 32860371
    INTRODUCTION: Differentiating between thalassaemia and iron deficiency anaemia (IDA) in hypochromic anaemia is a challenge to pathologists as it influences the choice of subsequent specialized confirmatory tests. In this study, we aimed to evaluate the performance of microcytic to hypochromic ratio (MicroR/ Hypo-He, M/H ratio) as a discriminant index in hypochromic anaemia.

    MATERIALS AND METHODS: A retrospective study was carried out on 318 subjects with hypochromic anaemia, which comprised 162 IDA and 156 thalassaemia trait subjects with α-thalassemia, β-thalassemia and HbE trait. Optimal cut-off value, sensitivity and specificity of M/H ratio for thalassaemia trait discrimination was determined using Receiver Operating Characteristic (ROC) analysis.

    RESULTS: Subjects with thalassaemia trait showed higher MicroR compared to IDA ( p< 0.001) while subjects with IDA demonstrated higher Hypo-He than thalassaemia trait (p < 0.001). M/H ratio was significantly higher in thalassaemia trait compared to IDA, with medians of 3.77 (interquartile range: 2.57 - 6.52) and 1.73 (interquartile range: 1.27 - 2.38), respectively (p < 0.001). M/H ratio ≥ 2.25 was the optimal cut-off value for discriminating thalassaemia trait from IDA in hypochromic anaemia, with the area under ROC curve (AUC) of 0.83, sensitivity of 80.8% and specificity of 71.6%.

    CONCLUSIONS: M/H ratio is a useful discriminant index to distinguish thalassaemia trait from IDA in hypochromic anaemia prior to diagnostic analysis for thalassaemia confirmation. High M/H ratio is suggestive of thalassaemia trait than of IDA. However, more studies are required to establish the role of M/H ratio as a screening tool for thalassaemia discrimination in hypochromic anaemia.

    Matched MeSH terms: beta-Thalassemia/diagnosis
  8. Fulltext Detection of α-thalassaemia in neonates on cord blood and dried blood spot samples by capillary electrophoresis
    Alauddin H, Langa M, Mohd Yusoff M, Raja Sabudin RZA, Ithnin A, Abdul Razak NF, et al.
    Malays J Pathol, 2017 Apr;39(1):17-23.
    PMID: 28413201 MyJurnal
    INTRODUCTION: Haemoglobin Bart's (Hb Bart's) level is associated with α-thalassaemia traits in neonates, enabling early diagnosis of α-thalassaemia. The study aimed to detect and quantify the Hb Bart's using Cord Blood (CB) and CE Neonat Fast Hb (NF) progammes on fresh and dried blood spot (DBS) specimen respectively by capillary electrophoresis (CE).

    METHODS: Capillarys Hemoglobin (E) Kit (for CB) and Capillarys Neonat Hb Kit (for NF) were used to detect and quantify Hb Bart's by CE in fresh cord blood and dried blood spot (DBS) specimens respectively. High performance liquid chromatography (HPLC) using the β-Thal Short Programme was also performed concurrently with CE analysis. Confirmation was obtained by multiplex ARMS Gap PCR.

    RESULTS: This study was performed on 600 neonates. 32/600 (5.3%) samples showed presence of Hb Bart's peak using the NF programme while 33/600 (5.5%) were positive with CB programme and HPLC methods. The range of Hb Bart's using NF programme and CB programme were (0.5-4.1%) and (0.5-7.1%), respectively. Molecular analysis confirmed all positive samples possessed α-thalassaemia genetic mutations, with 23/33 cases being αα/--SEA, four -α3.7/-α3.7, two αα/-α3.7 and three αα/ααCS. Fifty Hb Bart's negative samples were randomly tested for α-genotypes, three were also found to be positive for α-globin gene mutations. Thus, resulting in sensitivity of 91.7% and 88.9% and specificity of 100% for the Capillarys Cord Blood programme and Capillarys Neonat Fast programme respectively.

    CONCLUSION: Both CE programmes using fresh or dried cord blood were useful as a screening tool for α-thalassaemia in newborns. All methods show the same specificity (100%) with variable, but acceptable sensitivities in the detection of Hb Bart.
    Matched MeSH terms: beta-Thalassemia/diagnosis
  9. BamH1 polymorphism in the Chinese, Malays, and Indians in Singapore and its application in the prenatal diagnosis of beta-thalassemia
    Tan JA, Tay SH, Kham KY, Wong HB
    Jpn. J. Hum. Genet., 1993 Sep;38(3):315-8.
    PMID: 7903173 DOI: 10.1007/BF01874141
    The distribution of restriction fragment length polymorphism (RFLP) at the BamH1 site of the beta-globin gene was investigated in the Chinese, Indian, and Malay race in Singapore. The sample comprised of 183 normal individuals and 35 beta-thalassemia carriers in which 13 were couples with at least one beta-major child. The results from this study indicate that BamH1 polymorphism will be informative in 22% of pregnancies at risk for beta-thalassemia major in Chinese, 19% in Malays and 7% in Indians. In prenatal diagnosis using BamH1 polymorphism for one beta-major affected family, the fetus was diagnosed to be normal or beta-carrier. The validity of BamH1 polymorphism in the exclusion of beta-thalassemia major was subsequently confirmed at birth by globin chain biosynthesis.
    Matched MeSH terms: beta-Thalassemia/diagnosis*
  10. Fulltext Predictive SNPs for β0-thalassemia/HbE disease severity
    Munkongdee T, Tongsima S, Ngamphiw C, Wangkumhang P, Peerapittayamongkol C, Hashim HB, et al.
    Sci Rep, 2021 05 14;11(1):10352.
    PMID: 33990643 DOI: 10.1038/s41598-021-89641-2
    β-Thalassemia/HbE disease has a wide spectrum of clinical phenotypes ranging from asymptomatic to dependent on regular blood transfusions. Ability to predict disease severity is helpful for clinical management and treatment decision making. A thalassemia severity score has been developed from Mediterranean β-thalassemia patients. However, different ethnic groups may have different allele frequency and linkage disequilibrium structures. Here, Thai β0-thalassemia/HbE disease genome-wild association studies (GWAS) data of 487 patients were analyzed by SNP interaction prioritization algorithm, interacting Loci (iLoci), to find predictive SNPs for disease severity. Three SNPs from two SNP interaction pairs associated with disease severity were identifies. The three-SNP disease severity risk score composed of rs766432 in BCL11A, rs9399137 in HBS1L-MYB and rs72872548 in HBE1 showed more than 85% specificity and 75% accuracy. The three-SNP predictive score was then validated in two independent cohorts of Thai and Malaysian β0-thalassemia/HbE patients with comparable specificity and accuracy. The SNP risk score could be used for prediction of clinical severity for Southeast Asia β0-thalassemia/HbE population.
    Matched MeSH terms: beta-Thalassemia/diagnosis*
  11. [Simple and rapid analysis of beta-thalassemia mutation by sequence-specific amplification]
    Harano K, Harano T
    Rinsho Byori, 2013 Mar;61(3):217-23.
    PMID: 23785790
    This study was done to detect and diagnose beta-thalassemia (beta-Thal) gene quickly. We applied sequence specific Amplification (SSA) method to the analysis. 13 kinds of beta-Thal and two kinds of hemoglobin variants were able to detect under the same PCR condition. These mutations were found frequently in ten countries of Asian region (the southern part of China, Vietnam, Cambodia, Thailand, Myanmar, Malaysia, Singapore, Indonesia, Pakistan, India), and 15 kinds in total (-28CapA-->G, CD5-CT, CD8/9+-G, CD15G-->A, CD17A-->T, IVSI-1G-->T, CD41/42-4del, CD16-C, CD26G-->A(betaE), IVSI-5G-->C, CD35C-->A, CD71/72 +A, CD6A-->T (betaS), -619del, IVSII-654C-->T). More than 80% of patients are included in these mutations. To make the reagents a kit, the procedure became simple and rapid. DNA was extracted by salting out method. The PCR product was detected by polyacrylamide gel electrophoresis and silver staining. The confirmation of the variant was done by the PCR-direct sequencing method. It took approximately six hours for PCR reaction, electrophoresis and staining. This method made us to detect and diagnose beta-Thal in one day.
    Matched MeSH terms: beta-Thalassemia/diagnosis*
  12. Counseling for prenatal diagnosis and termination of pregnancy due to thalassemia major: a survey of health care workers' practices in Malaysia
    Ngim CF, Lai NM, Ibrahim H
    Prenat Diagn, 2013 Dec;33(13):1226-32.
    PMID: 24014379 DOI: 10.1002/pd.4233
    OBJECTIVE: Genetic counseling for thalassemia carriers is conducted by nongeneticist health care workers (HCWs) in many countries. The aim of the study was to assess Malaysian HCWs' genetic counseling practices with regards to discussing prenatal diagnosis (PND) and termination of pregnancy (TOP) when counseling thalassemia carriers.
    METHOD: A total of 118 Malaysian HCWs (52 doctors and 66 nurses) completed a structured questionnaire that enquired if they would discuss PND and TOP when counseling couples with thalassemia traits, and reasons for their responses were explored.
    RESULTS: All the nurses and 50 (96.1%) doctors were in favor of discussing PND. Only 29 (58%) doctors and 33 (50%) nurses were agreeable to discuss about the option of TOP. Main reasons given for declining to discuss TOP were views that "the condition was not serious enough" (54.9%), TOP is not permissible by their religion (17.6%) and abortion for this indication was illegal (13.7%).
    CONCLUSION: The results showed that HCWs in Malaysia lacked the comprehensive information and necessary skills required when counseling thalassemia carriers. When nongeneticist HCWs are tasked with such responsibilities, their practices and attitudes should be regularly evaluated so that areas of deficiencies could be identified and addressed.
    Matched MeSH terms: beta-Thalassemia/diagnosis*
  13. HbA2 levels in β-thalassaemia carriers with the Filipino β0-deletion: are the levels higher than what is found with non-deletional forms of β0-thalassaemia?
    George E, Teh LK, Tan J, Lai MI, Wong L
    Pathology, 2013 01;45(1):62-5.
    PMID: 23222244 DOI: 10.1097/PAT.0b013e32835af7c1
    AIMS: Classical carriers of β-thalassaemia are identified by a raised HbA2 level. Earlier studies indicated that the Filipino β-deletion has high raised HbA2 levels. The introduction of automated high performance liquid chromatography (HPLC) for thalassaemia screening is an important advance in technology for haematology laboratories. The BioRad Variant II Hb analyser is a common instrument used to quantify HbA2 levels in thalassaemia screening. This study aimed to determine HbA2 levels in carriers of Filipino β-mutation using the BioRad Variant II Hb analyser.

    METHODS: The Filipino β-deletion was identified using gap-polymerase chain reaction (PCR) in the parents of transfusion dependent β-thalassaemia patients who were homozygous for the Filipino β-deletion in the indigenous population of Sabah, Malaysia. Hb subtypes were quantified on the BioRad Variant II Hb analyser. Concurrent α-thalassaemia was identified by multiplex gap-PCR for deletions and amplification refractory mutation system (ARMS)-PCR for non-deletional mutations.

    RESULTS: The mean HbA2 level for Filipino β-thalassaemia trait was 5.9 ± 0.47 and with coinheritance of α-thalassaemia was 6.3 ± 0.44 (-α heterozygous) and 6.7 ± 0.36 (-α homozygous). The HbA2 levels were all >4% in keeping with the findings of classical β-thalassaemia trait and significantly higher than levels seen in non-deletional forms of β-thalassaemia.

    CONCLUSION: The HbA2 level measured on the BioRad Variant II Hb analyser was lower than the level in the first description of the Filipino β-thalassaemia. β-thalassaemia trait with coinheritance of α-thalassaemia (-α) is associated with significantly higher HbA2 level.

    Matched MeSH terms: beta-Thalassemia/diagnosis
  14. Fulltext Characterisation of beta-globin gene mutations in Malaysian children: a strategy for the control of beta-thalassaemia in a developing country
    Thong MK, Tan JA, Tan KL, Yap SF
    J Trop Pediatr, 2005 Dec;51(6):328-33.
    PMID: 15967770 DOI: 10.1093/tropej/fmi052
    beta-thalassaemia major, an autosomal recessive hemoglobinopathy, is one of the most common single gene disorders in multi-racial Malaysia. The control of beta-thalassaemia major requires a multi-disciplinary approach that includes population screening, genetic counselling, prenatal diagnosis and the option of termination of affected pregnancies. To achieve this objective, the molecular characterisation of the spectrum of beta-globin gene mutations in each of the affected ethnic groups is required. We studied 88 consecutive unrelated individuals and their respective families with beta-thalassaemia (74 beta-thalassaemia major, 12 HbE-beta-thalassaemia, 2 with HbE homozygotes) and four individuals with beta-thalassaemia trait that contributed a total 180 alleles for study. Using a 2-step molecular diagnostic strategy consisting of amplification refractory mutation system (ARMS) to identify the 8 most common mutations followed by other DNA-based diagnostic techniques, a total of 177 (98.3 per cent) of the 180 beta-thalassaemia alleles were characterised. One out of 91 (1 per cent) of the Chinese alleles, one out of 46 (2.2 per cent) Malay alleles and one out of two Indian alleles remained unknown. A 100 per cent success rate was achieved in studying the Kadazandusun community in this study. A strategy to identify beta-globin gene mutations in Malaysians with beta-thalassaemia is proposed based on this outcome.
    Matched MeSH terms: beta-Thalassemia/diagnosis
  15. A Rare Case of von Willebrand Disease Presenting as Hemolacria and Literature Review
    Nandakumal G, Ismail F, Mohamad NF, Lott PW, Chew KS, Ab Rahman S, et al.
    J Pediatr Hematol Oncol, 2021 04 01;43(3):101-103.
    PMID: 33560075 DOI: 10.1097/MPH.0000000000002077
    Hemolacria is a rare condition that causes a person to produce tears that are partially composed of blood. It can be a presenting feature of certain ocular and systemic conditions. Here, the authors describe an interesting case of a 12-year-old boy with an underlying beta-thalassemia trait, who presented with a 2-day history of bilateral blood-stained tears, and an episode of epistaxis. Ocular examination was normal, and syringing showed no nasolacrimal duct blockage. Systemic examination was unremarkable. Laboratory investigations confirmed type 2 von Willebrand disease. Management of hemolacria remains a clinical challenge given the rare occurrence of the disease. In this case report, the authors discuss the differential diagnosis and management approach to hemolacria.
    Matched MeSH terms: beta-Thalassemia/diagnosis
  16. The use of Taqman genotyping assays for rapid confirmation of β-thalassaemia mutations in the Malays: accurate diagnosis with low DNA concentrations
    Teh LK, Lee TY, Tan JA, Lai MI, George E
    Int J Lab Hematol, 2015 Feb;37(1):79-89.
    PMID: 24725998 DOI: 10.1111/ijlh.12240
    In Malaysia, β-thalassaemia is a common inherited blood disorder in haemoglobin synthesis with a carrier rate of 4.5%. Currently, PCR-incorporating techniques such as amplification refractory mutation system (ARMS) or reverse dot blot hybridization (RDBH) are used in β-thalassaemia mutation detection. ARMS allows single-mutation identification using two reactions, one for wild type and another for mutant alleles. RDBH requires probe immobilization and optimization of hybridization and washing temperatures which is time consuming. The aim of our study was to investigate whether β-thalassaemia mutations can be identified in samples with low DNA concentrations.
    Matched MeSH terms: beta-Thalassemia/diagnosis*
  17. An assessment of three noncommercial DNA extraction methods from dried blood spots for beta-thalassaemia mutation identification
    Karthipan SN, George E, Jameela S, Lim WF, Teh LK, Lee TY, et al.
    Int J Lab Hematol, 2011 Oct;33(5):540-4.
    PMID: 21884505 DOI: 10.1111/j.1751-553X.2011.01304.x
    Dried blood spots (DBS) are currently the recommended sample collection method for newborn screening programmes in America. Early diagnosis of beta-thalassaemia screening is essential as it provides an added advantage especially in sickle cell disease. Beta-thalassaemia frequency is high in many poor countries, and the cost of using commercial DNA extraction kits can be prohibitive. Our study assessed three methods that use minimal reagents and materials to extract DNA from DBS for beta-thalassaemia identification.
    Matched MeSH terms: beta-Thalassemia/diagnosis*
  18. Genotype-Phenotype Correlation of β-Thalassemia in Malaysian Population: Toward Effective Genetic Counseling
    Abdullah UYH, Ibrahim HM, Mahmud NB, Salleh MZ, Teh LK, Noorizhab MNFB, et al.
    Hemoglobin, 2020 May;44(3):184-189.
    PMID: 32586164 DOI: 10.1080/03630269.2020.1781652
    Effective prevention of β-thalassemia (β-thal) requires strategies to detect at-risk couples. This is the first study attempting to assess the prevalence of silent β-thal carriers in the Malaysian population. Hematological and clinical parameters were evaluated in healthy blood donors and patients with β-thal trait, Hb E (HBB: c.79G>A)/β-thal and β-thal major (β-TM). β-Globin gene sequencing was carried out for 52 healthy blood donors, 48 patients with Hb E/β-thal, 34 patients with β-TM and 38 patients with β-thal trait. The prevalence of silent β-thal carrier phenotypes found in 25.0% of healthy Malaysian blood donors indicates the need for clinician's awareness of this type in evaluating β-thal in Malaysia. Patients with β-TM present at a significantly younger age at initial diagnosis and require more blood transfusions compared to those with Hb E/β-thal. The time at which genomic DNA was extracted after blood collection, particularly from patients with β-TM and Hb E/β-thal, was found to be an important determinant of the quality of the results of the β-globin sequencing. Public education and communication campaigns are recommended as apparently healthy individuals have few or no symptoms and normal or borderline hematological parameters. β-Globin gene mutation characterization and screening for silent β-thal carriers in regions prevalent with β-thal are recommended to develop more effective genetic counseling and management of β-thal.
    Matched MeSH terms: beta-Thalassemia/diagnosis
  19. Combine-ARMS: a rapid and cost-effective protocol for molecular characterization of beta-thalassemia in Malaysia
    Tan KL, Tan JA, Wong YC, Wee YC, Thong MK, Yap SF
    Genet. Test., 2001;5(1):17-22.
    PMID: 11336396 DOI: 10.1089/109065701750168626
    Beta-thalassemia major patients have chronic anemia and are dependent on blood transfusions to sustain life. Molecular characterization and prenatal diagnosis of beta3-thalassemia is essential in Malaysia because about 4.5% of the population are heterozygous carriers for beta-thalassemia. The high percentage of compound heterozygosity (47.62%) found in beta-thalassemia major patients in the Thalassaemia Registry, University of Malaya Medical Centre (UMMC), Malaysia, also supports a need for rapid, economical, and sensitive protocols for the detection of beta-thalassemia mutations. Molecular characterization of beta-thalassemia mutations in Malaysia is currently carried out using ARMS, which detects a single beta-thalassemia mutation per PCR reaction. We developed and evaluated Combine amplification refractory mutation system (C-ARMS) techniques for efficient molecular detection of two to three beta-thalassemia mutations in a single PCR reaction. Three C-ARMS protocols were evaluated and established for molecular characterization of common beta-thalassemia mutations in the Malay and Chinese ethnic groups in Malaysia. Two C-ARMS protocols (cd 41-42/IVSII #654 and -29/cd 71-72) detected the beta-thalassemia mutations in 74.98% of the Chinese patients studied. The CARMS for cd 41-42/IVSII #654 detected beta-thalassemia mutations in 72% of the Chinese families. C-ARMS for cd 41-42/IVSI #5/cd 17 allowed detection of beta-thalassemia mutations in 36.53% of beta-thalassemia in the Malay patients. C-ARMS for cd 41-42/IVSI #5/cd 17 detected beta-thalassemia in 45.54% of the Chinese patients. We conclude that C-ARMS with the ability to detect two to three mutations in a single reaction provides more rapid and cost-effective protocols for beta-thalassemia prenatal diagnosis and molecular analysis programs in Malaysia.
    Matched MeSH terms: beta-Thalassemia/diagnosis*
  20. Thalassemia intermedia in HbH-CS disease with compound heterozygosity for beta-thalassemia: challenges in hemoglobin analysis and clinical diagnosis
    Tan JA, Kok JL, Tan KL, Wee YC, George E
    Genes Genet Syst, 2009 Feb;84(1):67-71.
    PMID: 19420802
    Co-inheritance of alpha-thalassemia with homozygosity or compound heterozygosity for beta-thalassemia may ameliorate beta-thalassemia major. A wide range of clinical phenotypes is produced depending on the number of alpha-thalassemia alleles (-alpha/alphaalpha --/alphaalpha, --/-alpha). The co-inheritance of beta-thalassemia with alpha-thalassemia with a single gene deletion (-alpha/alphaalpha) is usually associated with thalassemia major. In contrast, the co-inheritance of beta-thalassemia with two alpha-genes deleted in cis or trans (--/alphaalpha or -alpha/-alpha) generally produces beta-thalassemia intermedia. In Southeast Asia, the most common defect responsible for alpha-thalassemia is the Southeast Asian (SEA) deletion of 20.5 kilobases. The presence of the SEA deletion with Hb Constant Spring (HbCS) produces HbH-CS disease. Co-inheritance of HbH-CS with compound heterozygosity for beta-thalassemia is very rare. This study presents a Malay patient with HbH-CS disorder and beta degrees/beta+-thalassemia. The SEA deletion was confirmed in the patient using a duplex-PCR. A Combine-Amplification Refractory Mutation System (C-ARMS) technique to simultaneously detect HbCS and Hb Quong Sze confirmed HbCS in the patient. Compound heterozygosity for CD41/42 and Poly A was confirmed using the ARMS. This is a unique case as the SEA alpha-gene deletion in cis (--SEA/alphaalpha) is generally not present in the Malays, who more commonly possess the two alpha-gene deletion in trans (-alpha/-alpha). In addition, the beta-globin gene mutation at CD41/42 is a common mutation in the Chinese and not in the Malays. The presence of both the SEA deletion and CD41/42 in the mother of the patient suggests the possible introduction of these two defects into the family by marriage with a Chinese.
    Matched MeSH terms: beta-Thalassemia/diagnosis*
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