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  1. A link between long non-coding RNA (lncRNA) and thalassaemia: A review
    Sumera A, Radhakrishnan AK, Aziz Baba A, George E
    Malays J Pathol, 2020 Dec;42(3):323-332.
    PMID: 33361713
    The long non-coding RNAs (lncRNAs) are the most prevalent and functionally diverse member of the non-coding RNA (ncRNA). The lncRNA has previously been considered to be a form of transcriptional "noise" but recent studies have found that the lncRNA to be associated with various disease conditions. It has also been found to play important roles in various physiological processes such as haemopoiesis, where lncRNA is reported to act as a fine-tuner of this very important process. To date, the effects of dysregulated lncRNA in thalassaemia has not been fully explored. This review article focuses on the possible roles of dysregulated lncRNAs in the pathogenesis of thalassaemia.
    Matched MeSH terms: Thalassemia/genetics*
  2. Fulltext Thalassaemia and haemoglobinopathies in Brunei Darussalam
    Ismail JB
    Med J Malaysia, 1992 Jun;47(2):98-102.
    PMID: 1494340
    One thousand consecutive Brunei Darussalam patients referred with low Hb, and/or low MCV and MCH (Hb < 12.5g/dl, MCV < 76fl, MCH < 27pg) were studied in the laboratory for underlying haemoglobinopathies. 30.0% of such patients were proved to have either beta-thalassaemia trait, beta-thalassaemia major, Hb AE, Hb EE, Hb E beta-thalassaemia or Hb H disease. In some, the haemoglobin abnormality was not identified precisely. Alpha-thalassaemia was suspected in an additional 4.3% of cases but confirmation study by globin-chain synthesis was not available. Beta-thalassaemia trait which was the predominant disorder was equally distributed among the three major race groups of Brunei Darussalam. Hb E was found exclusive among the Malay population. Hb H disease appeared as more common among the Chinese or the Malays (p > 0.05). This study reveals that thalassaemia and haemoglobinopathies are prevalent in Brunei Darussalam.
    Matched MeSH terms: Thalassemia/genetics; beta-Thalassemia/genetics
  3. Interaction of haemoglobin E with alpha-thalassaemia and haemoglobin Constant Spring
    Ganesan J, Lie-Injo LE, Ng TS, George R
    Acta Haematol., 1977;57(2):109-15.
    PMID: 402765 DOI: 10.1159/000207867
    The combination of Hb E,alpha-thalassaemia and Hb CoSp was found in a 20-year-old female Malay who presented with a moderately severe haemolytic anaemia. The findings in the patient and her family from which this diagnosis was arrived at are discussed. Although this is the first report of this condition in this country it is pointed out that one may see more such cases in the future if one is aware of this condition since Hb E, alpha-thalassaemia and Hb CoSp all occur at significant frequencies in this country.
    Matched MeSH terms: Thalassemia/genetics*
  4. A commentary on molecular basis of transfusion dependent beta-thalassemia major patients in Sabah
    Setianingsih I
    J Hum Genet, 2014 Apr;59(4):173.
    PMID: 24500683 DOI: 10.1038/jhg.2013.142
    Matched MeSH terms: beta-Thalassemia/genetics*
  5. Fulltext Genotype-phenotype diversity of beta-thalassemia in Malaysia: treatment options and emerging therapies
    George E, Ann TJ
    Med J Malaysia, 2010 Dec;65(4):256-60.
    PMID: 21901940 MyJurnal
    The haemoglobinopathies and thalassemias represent the most common inherited monogenic disorders in the world. Beta-thalassaemia major is an ongoing public health problem in Malaysia. Prior to 2004, the country had no national policy for screening and registry for thalassemia. In the absence of a national audit, the true figure of the extent of thalassemia in the Malaysian population was largely presumptive from micro-mapping studies from various research workers in the country. The estimated carrier rate for beta-thalassemia in Malaysia is 3.5-4%. There were 4768 transfusion dependent thalassemia major patients as of May 2010 (Data from National Thalassemia Registry).
    Matched MeSH terms: beta-Thalassemia/genetics
  6. Mild homozygous high a2-type beta thalassaemia
    Ganesan J, Gill SS, Lie-Injo LE
    Med J Malaysia, 1974 Jun;28(4):229-33.
    PMID: 4278391
    Matched MeSH terms: Thalassemia/genetics*
  7. Hb lepore/β0-thalassaemia with α+-thalassaemia interactions, a potential diagnostic pitfall
    Alauddin H, Mohamad Nasir S, Ahadon M, Raja Sabudin RZ, Ithnin A, Hussin NH, et al.
    Malays J Pathol, 2015 Dec;37(3):287-92.
    PMID: 26712677
    Haemoglobin (Hb) Lepore is a variant Hb consisting of two α-globin and two δβ-globin chains. In a heterozygote, it is associated with clinical findings of thalassaemia minor, but interactions with other haemoglobinopathies can lead to various clinical phenotypes and pose diagnostic challenges. We reported a pair of siblings from a Malay family, who presented with pallor and hepatosplenomegaly at the ages of 21 months and 14 months old. The red cell indices and peripheral blood smears of both patients showed features of thalassaemia intermedia. Other laboratory investigations of the patients showed conflicting results. However, laboratory investigation results of the parents had led to a presumptive diagnosis of compound heterozygote Hb Lepore/β-thalassaemia and co-inheritance α+-thalassaemia (-α3.7). Hb Lepore has rarely been detected in Southeast Asian countries, particularly in Malaysia. These two cases highlight the importance of family studies for accurate diagnosis, hence appropriate clinical management and genetic counseling.
    Matched MeSH terms: alpha-Thalassemia/genetics*; beta-Thalassemia/genetics*
  8. Molecular Characterisation of α- and β-Thalassaemia among Indigenous Senoi Orang Asli Communities in Peninsular Malaysia
    Koh DXR, Raja Sabudin RZA, Mohd Yusoff M, Hussin NH, Ahmad R, Othman A, et al.
    Ann. Hum. Genet., 2017 Sep;81(5):205-212.
    PMID: 28620953 DOI: 10.1111/ahg.12201
    Thalassaemia is a public health problem in Malaysia, with each ethnic group having their own common mutations. However, there is a lack on data on the prevalence and common mutations among the indigenous people. This cross-sectional study was performed to determine the common mutations of α- and β-thalassaemia among the subethnic groups of Senoi, the largest Orang Asli group in Peninsular Malaysia. Blood samples collected from six Senoi subethnic groups were analysed for full blood count and haemoglobin analysis (HbAn). Samples with abnormal findings were then screened for α- and β-globin gene mutations. Out of the 752 samples collected, 255 showed abnormal HbAn results, and 122 cases showing abnormal red cell indices with normal HbAn findings were subjected to molecular screening. DNA analysis revealed a mixture of α- and β-globin gene mutations with 25 concomitant cases. The types of gene abnormalities detected for α-thalassaemia were termination codon (T>C) Hb CS (αCS α), Cd59 (G>A) haemoglobin Adana (Hb Adana) (αCd59 α), initiation codon (ATG>A-G) (αIniCd α), two-gene deletion (-SEA ), and single-gene 3.7-kb deletion (-α3.7 ). For β-thalassaemia, there were Cd26 (G>A) Hb E (βE ), Cd19 (A>G) Haemoglobin Malay (Hb Malay) (βCd19 ), and IVS 1-5 (G>C) (βIVS 1-5 ).
    Matched MeSH terms: alpha-Thalassemia/genetics*; beta-Thalassemia/genetics*
  9. Fulltext Molecular characterization of α- and β-thalassaemia among Malay patients
    Yatim NF, Rahim MA, Menon K, Al-Hassan FM, Ahmad R, Manocha AB, et al.
    Int J Mol Sci, 2014 May 19;15(5):8835-45.
    PMID: 24857915 DOI: 10.3390/ijms15058835
    Both α- and β-thalassaemia syndromes are public health problems in the multi-ethnic population of Malaysia. To molecularly characterise the α- and β-thalassaemia deletions and mutations among Malays from Penang, Gap-PCR and multiplexed amplification refractory mutation systems were used to study 13 α-thalassaemia determinants and 20 β-thalassaemia mutations in 28 and 40 unrelated Malays, respectively. Four α-thalassaemia deletions and mutations were demonstrated. --SEA deletion and αCSα accounted for more than 70% of the α-thalassaemia alleles. Out of the 20 β-thalassaemia alleles studied, nine different β-thalassaemia mutations were identified of which βE accounted for more than 40%. We concluded that the highest prevalence of (α- and β-thalassaemia alleles in the Malays from Penang are --SEA deletion and βE mutation, respectively.
    Matched MeSH terms: alpha-Thalassemia/genetics*; beta-Thalassemia/genetics*
  10. Molecular basis of transfusion dependent beta-thalassemia major patients in Sabah
    Teh LK, George E, Lai MI, Tan JA, Wong L, Ismail P
    J Hum Genet, 2014 Mar;59(3):119-23.
    PMID: 24369358 DOI: 10.1038/jhg.2013.131
    Beta-thalassemia is one of the most prevalent inherited diseases and a public health problem in Malaysia. Malaysia is geographically divided into West and East Malaysia. In Sabah, a state in East Malaysia, there are over 1000 estimated cases of β-thalassemia major patients. Accurate population frequency data of the molecular basis of β-thalassemia major are needed for planning its control in the high-risk population of Sabah. Characterization of β-globin gene defects was done in 252 transfusion dependent β-thalassemia patients incorporating few PCR techniques. The study demonstrates that β-thalassemia mutations inherited are ethnically dependent. It is important to note that 86.9% of transfusion-dependent β-thalassemia major patients in Sabah were of the indigenous population and homozygous for a single mutation. The Filipino β(0)-deletion was a unique mutation found in the indigenous population of Sabah. Mutations common in West Malaysia were found in 11 (4.3%) patients. Four rare mutations (Hb Monroe, CD 8/9, CD 123/124/125 and IVS I-2) were also found. This study is informative on the population genetics of β-thalassemia major in Sabah.
    Matched MeSH terms: beta-Thalassemia/genetics*
  11. Fulltext Distribution of alpha thalassaemia gene variants in diverse ethnic populations in malaysia: data from the institute for medical research
    Ahmad R, Saleem M, Aloysious NS, Yelumalai P, Mohamed N, Hassan S
    Int J Mol Sci, 2013;14(9):18599-614.
    PMID: 24025420 DOI: 10.3390/ijms140918599
    Alpha thalassaemia is highly prevalent in the plural society of Malaysia and is a public health problem. Haematological and molecular data from 5016 unrelated patients referred from various hospitals to the Institute for Medical Research for α thalassaemia screening from 2007 to 2010 were retrieved. The aims of this retrospective analysis were to describe the distribution of various alpha thalassaemia alleles in different ethnic groups, along with their genotypic interactions, and to illustrate the haematological changes associated with each phenotype. Amongst the patients, 51.2% (n = 2567) were diagnosed with α thalassaemia. Of the 13 α thalassaemia determinants screened, eight different deletions and mutations were demonstrated: three double gene deletions, --(SEA), --(THAI), --(FIL); two single-gene deletions, α-³·⁷ and -α⁴·²; and three non-deletion mutations, Cd59G > A (haemoglobin [Hb] Adana), Cd125T > C (Hb Quong Sze) and Cd142 (Hb Constant Spring). A high incidence of α-³·⁷ deletion was observed in Malays, Indians, Sabahans, Sarawakians and Orang Asli people. However, the --SEA deletion was the most common cause of alpha thalassaemia in Chinese, followed by the α-³·⁷ deletion. As many as 27 genotypic interactions showed 1023 α thalassaemia silent carriers, 196 homozygous α⁺ thalassaemia traits, 973 heterozygous α⁰ thalassaemia carriers and 375 patients with Hb H disease. Statistical analysis showed a significant difference in the distribution of α thalassaemia determinants amongst the various ethnic groups. Hence, the heterogeneous distribution of common determinants indicated that the introduction of an ethnicity-targeted hierarchical α thalassaemia screening approach in this multi-ethnic Malaysian population would be effective.
    Matched MeSH terms: alpha-Thalassemia/genetics*
  12. [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/genetics
  13. Molecular study and genotype/phenotype correlation of β Thalassemia in Malaysia
    Sivalingam M, Looi ML, Zakaria SZ, Hamidah NH, Alias H, Latiff ZA, et al.
    Int J Lab Hematol, 2012 Aug;34(4):377-82.
    PMID: 22335963 DOI: 10.1111/j.1751-553X.2012.01405.x
    INTRODUCTION: To study the ß-gene mutations spectrum, the genotype/phenotype correlation, the modulatory effect of co-inherited factors such as α-gene mutations and of Xmn1 polymorphism in a large cohort of Malaysian patients.
    METHODS: A total of 264 cases clinically diagnosed as Thalassemia major (TM) (111), Thalassemia intermedia (21), HbE-β Thalassemia (131), and 1 HbE homozygous were studied. The detection of α and ß gene mutations and characterization of Xmn1 polymorphism were performed by multiplex PCR, amplification refractory mutation system (ARMS), DNA sequencing, and restriction fragment length polymorphism (RFLP)-PCR.
    RESULTS: A total of 19 ß Thalassemia mutations were characterized. CD26 and CD41/42 were the most common found in the Malay and Chinese population, respectively. The sensitivity of the clinical diagnosis for β TM, thalassemia intermedia, and HbE/β thalassemia was 94.0%, 15.2%, and 89.2%, respectively. Patients with Xmn1 heterozygosity [+/-] required less frequent transfusion compared with those without the polymorphism. Co-inheritance of α-thalassemia alleviates the severity of HbE-β thalassemia in our cohort.
    CONCLUSION: Molecular analysis should be used for a better diagnosis and management of β thalassemia.
    Matched MeSH terms: beta-Thalassemia/genetics*
  14. Fulltext A rare case of alpha-thalassaemia intermedia in a Malay patient double heterozygous for alpha(+)-thalassaemia and a mutation in alpha1 globin gene CD59 (GGC --> GAC)
    George E, Jama T, Azian AS, Rahimah A, Zubaidah Z
    Med J Malaysia, 2009 Dec;64(4):321-2.
    PMID: 20954559
    A rare case of thalassaemia-intermedia involving a non-deletion alpha thalassemia point mutation in the alpha1-globin gene CD59 (GGC --> GAC) and a deletion alpha+ (-alpha(3.7)) thalassaemia in which use of high performance liquid chromatography (HPLC) C-gram Hb subtype profile and DNA molecular analysis helped establish the diagnosis.
    Matched MeSH terms: alpha-Thalassemia/genetics*
  15. Fulltext Analysis of α1 and α2 globin genes among patients with hemoglobin Adana in Malaysia
    Lee TY, Lai MI, Ismail P, Ramachandran V, Tan JA, Teh LK, et al.
    Genet. Mol. Res., 2016 Apr 07;15(2).
    PMID: 27173219 DOI: 10.4238/gmr.15027400
    Hemoglobin (Hb) Adana [HBA2: c179G>A (or HBA1); p.Gly60Asp] is a non-deletional α-thalassemia variant found in Malaysia. An improvement in the molecular techniques in recent years has made identification of Hb Adana much easier. For this study, a total of 26 Hb Adana α-thalassemia intermedia and 10 Hb Adana trait blood samples were collected from patients. Common deletional and non-deletional α-thalassemia genotypes were determined using multiplex gap polymerase chain reaction (PCR) and multiplex ARMS PCR techniques. Identification of the Hb Adana location on the α-globin gene was carried out using genomic sequencing and the location of the mutation was confirmed via restriction fragment length polymorphism-PCR. Among the 36 samples, 24 (66.7%) had the -α(3.7)/α(Cd59)α mutation, while the -α(3.7)/α(Cd59)α mutation accounted for 2 samples (5.6%) and the remaining 10 (27.8%) samples were α/α(Cd59)α. All 36 samples were found to have the Hb Adana mutation on the α2-globin gene. The position of the α-globin gene mutation found in our cases was similar to that reported in Indonesia (16%) but not to that in Turkey (0.6%). Our results showed that the Hb Adana mutation was preferentially present in the α2-globin genes in Malays compared to the other ethnicities in Malaysia. Thus, the Malays might have similar ancestry based on the similarities in the Hb Adana position.
    Matched MeSH terms: alpha-Thalassemia/genetics*
  16. A single, large deletion accounts for all the beta-globin gene mutations in twenty families from Sabah (North Borneo), Malaysia. Mutation in brief no. 240. Online
    Thong MK, Rudzki Z, Hall J, Tan JA, Chan LL, Yap SF
    Hum Mutat, 1999;13(5):413.
    PMID: 10338100 DOI: 10.1002/(SICI)1098-1004(1999)13:5<413::AID-HUMU15>
    Beta-thalassemia major is one of the commonest genetic disorders in South-East Asia. The spectrum of beta-thalassemia mutations in the various ethnic sub-populations on the island of Borneo is unknown. We studied 20 Dusun children from the East Malaysian state of Sabah (North Borneo) with a severe beta-thalassemia major phenotype, using a combination of Southern analysis, polymerase chain reaction analysis and direct sequencing. We found the children to be homozygous for a large deletion, which has a 5' breakpoint at position -4279 from the cap site of the beta-globin gene (HBB) with the 3' breakpoint located in a L1 family of repetitive sequences at an unknown distance from the beta-globin gene. This was similar to a recent finding of a large deletion causing beta-thalassemia first described in unrelated beta-thalassemia heterozygotes of Filipino descent. This report describes the first 20 families with homozygosity of the deletion causing a severe phenotype. It provides the first information on the molecular epidemiology of beta-thalassemia in Sabah. This finding has implications for the population genetics and preventative strategies for beta-thalassemia major for nearly 300 million individuals in South-East Asia.
    Matched MeSH terms: beta-Thalassemia/genetics*
  17. Fulltext Beta-thalassemia major in Malaysia, an ongoing public health problem
    George E
    Med J Malaysia, 2001 Dec;56(4):397-400.
    PMID: 12014756
    Matched MeSH terms: beta-Thalassemia/genetics*
  18. Alpha-hemoglobin-stabilizing protein (AHSP): a modulatory factor in β-thalassemia
    Che Yaacob NS, Islam MA, Alsaleh H, Ibrahim IK, Hassan R
    Int J Hematol, 2020 Mar;111(3):352-359.
    PMID: 31894534 DOI: 10.1007/s12185-019-02806-8
    Hemoglobin (Hb) is an iron-containing metalloprotein that transports oxygen molecules from the lungs to the rest of the human body. Among the different variants of Hb, HbA1 is the most common and is composed of two alpha (αHb) and two beta globin chains (βHb) constructing a heterotetrameric protein complex (α2β2). Due to the higher number of AHSP genes, there is a tendency to produce approximately twice as much of α subunit as β subunit. Therefore, there is a chance of presenting excess α subunit leftover in human blood plasma; excess subunits subsequently bind with each other and aggregates β-thalassemia occurs due to lack of or reduced numbers of βHb subunit. Alpha-hemoglobin-stabilizing protein (AHSP) is a scavenger protein which acts as a molecular chaperon by reversibly binding with free αHb forming a complex (AHSP-αHb) that prevents aggregation and precipitation preventing deleterious effects towards developing serious human diseases including β-thalassemia. Clinical severity worsens if mutations in AHSP gene co-occur in patients with β-thalassemia. Considering the mechanism of action of AHSP and its contribution to ameliorating β-thalassemia severity, it could potentially be used as a modulatory agent in the treatment of β-thalassemia.
    Matched MeSH terms: beta-Thalassemia/genetics*
  19. Fulltext Comparison of gene mutation spectrum of thalassemia in different regions of China and Southeast Asia
    Yang Z, Cui Q, Zhou W, Qiu L, Han B
    Mol Genet Genomic Med, 2019 06;7(6):e680.
    PMID: 30968607 DOI: 10.1002/mgg3.680
    BACKGROUND: Thalassemia is a common genetic disorder. High prevalence of thalassemia is found in South China, Southeast Asia, India, the Middle East, and the Mediterranean regions. Thalassemia was thought to exist only in southern China, but an increasing number of cases from northern China have been recently reported.

    METHODS: During 2012 to 2017, suspected thalassemia people were detected for common α- and β-thalassemia mutations by gap-Polymerase Chain Reaction (PCR) and reverse dot blot (RDB) analysis in Peking Union Medical College Hospital. One thousand and fifty-nine people with thalassemia mutations were analyzed retrospectively. We picked mutated individuals who originally came from northern areas, and conducted telephone follow-up survey in order to collect their ancestral information. Besides, we used "thalassemia", "mutation", and "Southeast Asian countries" as keywords to search the relevant studies in PubMed and Embase databases.

    RESULTS: All carriers included in our study were resided in northern China. Among them, 17.3% were native northerners and 82.7% were immigrants from southern China. Although substantial difference was found in α- and β-thalassemia ratio and detailed spectrum of α- and β-globin mutation spectrum between our data and data obtained from a previous meta-analysis literature focused on southern China, the most common gene mutations were the same. Similar β-thalassemia mutation spectrum was found among Thai, Malaysian Chinese, and Guangdong people, however, no other similarities in gene profile were found between Chinese and other ethnic groups in Southeast Asia.

    CONCLUSION: Chinese people in different areas had similar gene mutation, whereas they had significantly different mutation spectrums from other ethnic groups in Southeast Asia.

    Matched MeSH terms: Thalassemia/genetics*
  20. Hb E-beta thalassaemia in the West Malaysian Orang Asli (aborigines)
    Bolton JM, Lie-Injo Luan Eng
    Med J Malaya, 1969 Sep;24(1):36-40.
    PMID: 4244260
    Matched MeSH terms: Thalassemia/genetics
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