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  1. Fulltext Cytogenetic study of Malaysian neonates with congenital abnormalities in Maternity Hospital Kuala Lumpur
    Norlasiah IS, Clyde MM, Boo NY
    Med J Malaysia, 1995 Mar;50(1):52-8.
    PMID: 7752977
    During the period 1 January 1990-31 December 1990, 68 neonates with congenital abnormalities were successfully analysed for chromosome abnormalities in order to determine the contribution of chromosome aberrations to the aetiology of congenital abnormalities. The neonates were karyotyped employing the G-banding technique. Twenty-nine babies showed abnormal chromosome karyotypes. Twenty-six were observed to have classic trisomy syndromes; ie. trisomy 21 (32.3%), trisomy 18 (3.0%), and trisomy 13 (3.0%). The mean maternal age of the mothers with babies having normal karyotype was lower than the mean maternal age of the mothers having babies with abnormal karyotypes. From this study the incidence of congenital abnormalities due to chromosomal abnormalities is found to be 1:838 livebirths. Frequency of newborns having abnormal chromosomes is 0.14% for Malays, 0.12% for Chinese and 0.06% for Indians.
    Matched MeSH terms: Cytogenetics/methods*
  2. Fulltext Cytogenetics: past, present and future
    Kannan TP, Zilfalil BA
    Malays J Med Sci, 2009 Apr;16(2):4-9.
    PMID: 22589651 MyJurnal
    Fifty years have elapsed since the discovery of the number of human chromosomes in 1956. Newer techniques have been developed since then, ranging from the initial conventional banding techniques to the currently used molecular array comparative genomic hybridisation. With a combination of these conventional and molecular techniques, cytogenetics has become an indispensable tool for the diagnosis of various genetic disorders, paving the way for possible treatment and management. This paper traces the history and evolution of cytogenetics leading up to the current state of technology.
    Matched MeSH terms: Cytogenetics
  3. Fulltext Optimization of the cytogenetic protocol for Pangasianodon hypophthalmus (Sauvage, 1878) and Clarias gariepinus (Burchell, 1822)
    Okomoda VT, Koh ICC, Hassan A, Amornsakun T, Moh JHZ, Shahreza SM
    PeerJ, 2018;6:e5712.
    PMID: 30416879 DOI: 10.7717/peerj.5712
    To obtain well spread chromosomes, the cytogenetic protocol for Pangasianodon hypophthalmus and Clarias gariepinus were optimized. This includes, the colchicine concentration (0.01%, 0.025%, 0.05%)/exposure duration (1, 3, and 5 h), hypotonic solution (distilled water or 0.075M KCl solution)/exposure duration (30 min, 1, and 2 h), the time of cell suspension preparation (at hypotonic treatment or before slide preparation) and chromosome aging period (0, 3, and 7 days in Carnoy's fixative). In addition, the type (i.e., fin, gill or kidney) and the amount of tissue (10, 50, 100 or 150 mg) were also investigated. Regardless of the species, the result obtained showed that well-spread chromosomes could be obtained using the following optimized protocol: Juveniles are injected with 0.05% colchicine (at one ml kg-1) and allowed to swim for 3 h. Then, 50 mg of gill tissue is made into cell suspension in 0.075M KCl for 1 h. The cell suspension is treated in Carnoy's fixative (changed three times at 20 min interval) and then aged for 3 days. Finally, chromosome slides are made and stained with 10% Giemsa for 1 h.
    Matched MeSH terms: Cytogenetics
  4. Maternal blood : potential use in prenatal screening and diagnostics
    Karuppiah, Thilakavathy, Jammal Ahmad Essa, Rozita Rosli
    Buletin Persatuan Genetik Malaysia, 2002;8(1):0-0.
    MyJurnal
    Smaller family size and advancing parental age have increased the demand for prenatal diagnosis.
    Prenatal cytogenetic diagnoses currently used, such as amniocentesis and chorionic villus
    sampling, are usually not preferred by the expectant couples due to the risk imposed on the mother and child. High false positive rates (5%) of current non-invasive screening methods, such as serum analysts or ultrasound, cause a large number of unnecessary invasive practices to be performed, which apart from the associated risk, place considerable psychological distress on the couples
    involved (Wald et al., 1999). (Copied from article).
    Matched MeSH terms: Cytogenetics
  5. Chromosome polymorphism in the Malayan house shrew, Suncus murinus (Insectivora, Soricidae)
    Yong HS
    Experientia, 1971 May 15;27(5):589-91.
    PMID: 5132609
    Matched MeSH terms: Cytogenetics
  6. Fulltext The various effect s of Nigella sativa on multiple body systems in human and animals
    Mohammed Abdulrazzaq Assi
    The Pertanika Journal of Scholarly Research Reviews, 2016;2(3):0-0.
    MyJurnal
    Nigella sativa (Black seeds) has been recognized as one of the most popular herbs in many
    parts of the world for centuries. It was used in the world as folk medicine to cure different kinds of diseases. This plant has been considered as one of the main sources of nutrition and healthcare for humans as well as animals. It has been perceived as Kalonji; it is a southwest Asian plan t that flowers annually. The seeds and oil of this plant have been used in food; in addition, it has a long history in the making of medicines. In addition to its being a model plant for better realization of gene and chromosome relationship, the plant species is also significant cytogenetically. Plant based system has not been absorbed fully for human health care despite the remarkable advancements in the field of pharmacology. Cumin, as one of the medicinal plants gifted to humans by nature, has a number of potential uses. It has been proved to be a
    useful herbal medicines that can be used for human health and therefore has been extensively studied and investigated to further discover the advantages of this plant.
    Matched MeSH terms: Cytogenetics
  7. Genotoxic effect of zinc and cadmium following single and binary mixture exposures in tilapia (oreochromis niloticus) using micronucleus test
    Abu Bakar S, Ashriya A, Shuib A, Razak S
    Sains Malaysiana, 2014;43:1053-1059.
    The aim of this study was to investigate the genotoxicity effect of Cd and Zn and their binary mixtures in tilapia fish Oreochromis niloticus using the micronucleus test. Two cytogenetic end points were considered; the frequencies of micronucleated cells and nuclear abnormalities. Fishes were exposed to 4.63 mg/L Cd, 7.50 mg/L Zn and 4.63 mg/L Cd + 7.50 mg/L Zn mixture for the period of 24, 48, 72 and 96 h. The results showed that the frequencies of micronuclei and nuclear abnormalities in the erythrocyte were significantly increased in all groups of treatments when compared with the control group (0 exposures). In addition, the highest frequencies of micronucleated and nuclear abnormalities were obtained after 48 h exposure in almost all cases (except in the mixture of Cd+Zn) and decreased after 72 and 96 h exposure. Frequencies of micronuclei and erythrocytes with nuclear abnormalities exposed to a mixture of Cd+Zn in O. niloticus were always lower at all-time points (after 24, 48, 72 and 96 h) than that of a single Cd and Zn exposure. Therefore, the study demonstrated that the genotoxic potential of these metal compounds and the simultaneous treatment of Cd and Zn suggest the presence of antagonistic interactions.
    Matched MeSH terms: Cytogenetics
  8. Fulltext Detection of bcr/abl gene in chronic myeloid leukaemia: comparison of fluorescence in situ hybridisation (fish), conventional cytogenetics and polymerase chain reaction (pcr) techniques
    Siti Aishah Md Ali, Ilina Isahak, Dahlan Sabil, Fatimah Sahlan, Lokman Saim, Abdullah Sani Mohamed
    Medicine & Health, 2006;1(1):5-13.
    MyJurnal
     
    The reciprocal translocation t(9;22)(q34;q11) which gives rise to the Philadelphia (Ph1) chromosome and BCR/ABL fusion gene, plays a pivotal role in the diagnosis and pathogenesis of chronic myeloid leukemia (CML). In this study, we evaluated the role of fluorescence in situ hybridisation (FISH) in detecting the BCR/ABL rearrangement in CML patients. The sensitivity, specificity and detection rate of BCR/ABL gene using FISH, PCR and conventional cytogenetics (karyotyping) methods were also compared. 18 bone marrow samples of patients with clinically diagnosed CML and suspected of CML were collected. The sensitivity, specificity and positive predictive values of FISH were altogether 100% while the sensitivity, specificity and positive predictive values for conventional cytogenetics (karyotyping) were 85%, 100% and 100% respectively. Convetional cytogenetics (karyotyping) detected an additional chromosomal aberration in addition to the Ph1 chromosome. In conclusion, FISH is a highly sensitive method in detecting the BCR/ABL gene. Conventional cytogenetics (karyotyping) remains an important investigation in the work up of suspected CML patients since there is a possibility of detecting chromosomal aberrations in addition to the Ph1 translocation. Therefore, conventional cytogenetics (karyotyping) and FISH are complementary techniques and their results should be interpreted together with clinical information.
    Matched MeSH terms: Cytogenetics
  9. Fulltext Identification of Y Chromosomal Material in Turner Syndrome by Fluorescence In Situ Hybridisation (FISH)
    Reena Rahayu Md Zin, Sharifah Noor Akmal, Zubaidah Zakaria, Haut, Clarence Ko Ching, Siti Mariam Yusof, Julia Mohd Idris, et al.
    Medicine & Health, 2008;3(1):22-29.
    MyJurnal
    Turner syndrome is one of the most common chromosomal abnormalities affecting newborn females. More than half of patients with Turner syndrome have a 45X karyotype The rest of the patients may have structurally abnormal sex chromosomes or are mosaics with normal or abnormal sex chromosomes. Mosaicism with a second X sex chromosome is not usually of clinical significance. However, Turner syndrome patients having a second Y chromosome or Y chromosomal material are at risk of developing gonadoblastoma later in life. The aim of this study is to compare the results of conventional (karyotyping) and molecular cytogenetics (FISH), and discuss the advantages and limitations in the diagnosis of Turner syndrome. We also aim to compare the degree of mosaicism identified using conventional cytogenetics and FISH techniques. Conventional cytogenetics and FISH analyses were performed on eight peripheral blood samples of patients with Turner syndrome collected between 2004 and 2006. From this study, two out of eight patients with Turner syndrome were found to have the sex determining region on the Y chromosome (SRY) gene by FISH analysis. Our results showed that the rate of detection of mosaic cases in Turner syndrome was also increased to 88% after using the FISH technique. We concluded that FISH is more superior to conventional cytogenetics in the detection of the Y chromosomal material. FISH is also a quick and cost effective method in diagnosing Turner syndrome and assessing the degree of mosaicism.
    Matched MeSH terms: Cytogenetics
  10. Fulltext Complex chromosomal rearrangement der(5)ins(5;3)(q31;q25q29), t(3;12)(q24;p12.2) in a dysmorphic child, - a case report
    Aziati Azwari Annuar, Nik Mohd Zulfikri Mat Zin, Siti Mariam Ismail, Nurul Alia Mohd Nawi, Nazihah Mohd Yunus, Sarina Sulong, et al.
    Journal of Biomedical and Clinical Sciences, 2017;2(202):3-5.
    MyJurnal
    Complex chromosome rearrangements (CCRs) are structural aberrations or rearrangements involving three or more cytogenetics breakpoints on two or more chromosomes [1]. Balanced and unbalanced are known to have significant risk of mental retardation and phenotypic anomalies. CCRs are also associated with infertility in males and recurrent abortion in females. Here we report one case of apparently balanced CCR involving three chromosomes 3, 5 and 12 in a child with abnormal features. G banding and FISH were performed to clarify the nature of this complex abnormality.
    Matched MeSH terms: Cytogenetics
  11. Fulltext Exploring Two Protocols of FISH Using Cytocell SYT-SSX Probe on Formalin Fixed Paraffin Embedded Tissue Sections
    Yajid AI, Mohd Nafi SN, Salehan NA, Tuan Sharif SE
    Asian Pac J Cancer Prev, 2020 May 01;21(5):1241-1245.
    PMID: 32458628 DOI: 10.31557/APJCP.2020.21.5.1241
    BACKGROUND: Chromosomal translocation t(X;18)(p11.2;q11.2) is the cytogenetic hallmark of synovial sarcoma and have been identified as an alternative diagnostic strategy in differentiating synovial sarcoma from other histologic mimics. This study was carried out to test the efficacy of two FISH protocols using the SYT-SSX break apart probe from Cytocell.

    METHODOLOGY: Representative paraffin blocks of synovial sarcoma were utilized in this study. FISH study was performed on formalin-fixed paraffin embedded tissue sections using the SYT-SSX break apart probe from Cytocell, to detect two form of SYT-SSX transcript, SYT-SSX1 and SYT-SSX2. FISH protocol, including the hybridization was done following two different protocols, Cytocell FISH protocol and Optimized Dako FISH protocol.

    RESULTS: Tissue samples subjected to FISH using Cytocell FISH protocol showed the absence of signal corresponding to the probe used. Utilizing Optimized Dako FISH protocol, the two signals (red and green) corresponding to the break-apart probes was detected. These findings suggested that Optimised Dako FISH protocol is more suited for use with the tested probe on paraffin embedded tissues in comparison to Cytocell FISH protocol.

    CONCLUSION: Optimised Dako FISH protocol was noted to be more suited for detecting SYT-SSX FISH signals on paraffin embedded tissues in comparison to Cytocell FISH protocol.

    Matched MeSH terms: Cytogenetics
  12. Fulltext Differential Analysis of Genetic, Epigenetic, and Cytogenetic Abnormalities in AML
    Islam M, Mohamed Z, Assenov Y
    Int J Genomics, 2017;2017:2913648.
    PMID: 28713819 DOI: 10.1155/2017/2913648
    Acute myeloid leukemia (AML) is a haematological malignancy characterized by the excessive proliferation of immature myeloid cells coupled with impaired differentiation. Many AML cases have been reported without any known cytogenetic abnormalities and carry no mutation in known AML-associated driver genes. In this study, 200 AML cases were selected from a publicly available cohort and differentially analyzed for genetic, epigenetic, and cytogenetic abnormalities. Three genes (FLT3, DNMT3A, and NPMc) are found to be predominantly mutated. We identified several aberrations to be associated with genome-wide methylation changes. These include Del (5q), T (15; 17), and NPMc mutations. Four aberrations-Del (5q), T (15; 17), T (9; 22), and T (9; 11)-are significantly associated with patient survival. Del (5q)-positive patients have an average survival of less than 1 year, whereas T (15; 17)-positive patients have a significantly better prognosis. Combining the methylation and mutation data reveals three distinct patient groups and four clusters of genes. We speculate that combined signatures have the better potential to be used for subclassification of AML, complementing cytogenetic signatures. A larger sample cohort and further investigation of the effects observed in this study are required to enable the clinical application of our patient classification aided by DNA methylation.
    Matched MeSH terms: Cytogenetics
  13. Fulltext Protein and gene expression of leukemia stem cells markers in acute myeloid leukemia
    Amrina Mohamad Amin, Maha Abdullah, Sabariah Md Noor, Raudhawati Osman, Wan Hayati Mohd Yaacob, Cheong Soon Keng
    Malaysian Journal of Medicine and Health Sciences, 2019;15(108):23-23.
    MyJurnal
    Introduction: Acute myeloid leukaemia (AML) is a clonal haematological neoplasm characterised by proliferation of immature myeloid cells in the bone marrow resulting in impairment normal cell development in bone marrow. This leads to anaemia, thrombocytopenia and neutropenia. AML primarily affects older adults, with a median age at diagnosis of 69 years but is also seen in all other age groups. AML is recognized as a kind of cancer with marked heterogeneity in both biology of the cells and reactions to treatment. Treatment with intensive chemotherapy regi-mens of adult AML patients who are ≤ 60 years old results in hematologic remission in about 35% of patients, but at least 30% of these patients will experience a relapse. Mechanism leading to early relapse is still unclear. Leukaemia stem cell (LSC) is shown to correlate with poor prognosis. Biomarkers such as aldehyde dehydrogenase (ALDH) and CD34+CD38- have been identified as potential LSC biomarkers in previous studies. The objective of this study is to examine the expression of such markers for LSC and determine the association. Methods: Peripheral blood or bone marrow samples from untreated, newly diagnosed acute myeloid leukemias of all age, gender and race were collect-ed from Hospital Melaka and Kelang. Diagnosis of AML is based on WHO classification which include morphology, cytochemistry, immunophenotyping and cytogenetics. Mononuclear cells were isolated from bone marrow aspirate samples by gradient density centrifugation on Ficoll-Hypaque. Immunophenotyping using CD13, CD14, CD33, CD34, CD38 and ALDH were carried out to identify the presence and proportion of the various populations of inter-est. Results: There was a strong, positive correlation between ALDH and CD34+CD38- cell population, which was statistically significant (rs = 0.5989, p< 0.05). Conclusion: The strong correlation of ALDH activity and CD34+CD38- expression supported the potential of these biomarkers to identify LSCs cell in AML patients. However, due to the heterogeneity of AML, further studies using more markers and larger sample size are needed to determine the validity and to correlate with disease-free survival rate of AML patients.
    Matched MeSH terms: Cytogenetics
  14. Fulltext The role of conventional and molecular cytogenetics in the diagnosis of microdeletion syndromes
    Salwati Shuib, Sharifah Noor Akmal, Zarina Abdul Latif, Nor Zarina Zainal Abidin, Zubaidah Zakaria
    Medicine & Health, 2006;1(1):45-52.
    MyJurnal
    In this report we demonstrate the role of fluorescence in situ hybridisation (FISH) and conventional cytogenetic methods in clinically and cytogenetically confirmed cases of microdeletion syndromes. A total of nine cases were referred to the Cytopathology and Cytogenetic Unit, Hospital Universiti Kebangsaan Malaysia (HUKM) from 2002 to 2004. They include three Prader-Willi syndrome, three DiGeorge syndrome, one Williams syndrome, one Miller-Dieker syndrome and one Kallmann syndrome. Blood samples from the patients were cultured and harvested following standard procedures. Twenty metaphases were analysed for each of the cases. FISH analysis was carried out for all the cases using commercial probes (Vysis, USA): SNRPN and D15S10 for Prader-Willi syndrome, LIS1 for Miller Dieker syndrome, ELN for Williams syndrome, KAL for Kallmann syndrome, TUPLE 1 and D22S75 for DiGeorge syndrome. Conventional cytogenetic analysis revealed normal karyotypes in all but one case with structural abnormality involving chromosomes 9 and 22. FISH analysis showed microdeletions in all of the nine cases studied. This study has accomplished two important findings ie. while the FISH method is mandatory in ruling out microdeletion syndromes, conventional cytogenetics acts as a screening tool in revealing other chromosomal abnormalities that may be involved with the disease.
    Matched MeSH terms: Cytogenetics
  15. Fulltext Cytogenetic analysis of buccal cells from farmers in Tanjung Karang and Kelantan who were exposed to pesticides
    Ahmad Rohi Ghazali, Maziani Abdullah, Asmah Hamid, Asmariah Ahmad, Tava Shelan Nagapan, Ismarulyusda Ishak, et al.
    Jurnal Sains Kesihatan Malaysia, 2018;16(101):1-8.
    MyJurnal
    Pesticides and chemical fertilizers are widely used in agriculture to increase crop productivity among farmers. However, exposure to pesticides will give potential risk to human health. The aim of this study was to analyze the frequency of micronucleus (MN) and binucleus (BNu) formation in buccal cells from farmers who were exposed to pesticides using the MN assay. Buccal swabs were collected from the farmers in Tanjung Karang (n = 32) and Kelantan (n = 43) using wooden tongue depressor. A structured questionnaire was used to obtain demographic data of the farmers. Cytogenetic analysis was carried out by Acridin Orange (AO) staining 0.0025% (w/v). The frequency of MN and BNu as the biomarkers for cytogenetic damage was observed by using a fluorescence microscope. Comparison of frequency of MN and BNu is conducted in two areas namely Tanjung Karang, Selangor and Kelantan because of the agricultural activity and the type of pesticides used are different. Results showed that the frequencies of both MN and BNu among farmers in Tanjung Karang were significantly higher (p < 0.05) compared to farmers in Kelantan. Meanwhile, for the socio-demographic factors (age, smoking status, working period), MN and BNu frequencies among farmers in Tanjung Karang were also significantly higher (p < 0.05) as compared to farmers in Kelantan. While in the aspect of pesticide exposure, the frequencies of MN and BNu showed no significant difference between the frequency of pesticide spraying (p > 0.05) and the practices of PPE (Personal Protective Equipment) (p > 0.05). This may suggests that cytogenetic changes were not influenced by these factors. In addition, correlation study shows positive correlation between the frequency of MN with the pesticide exposure of farmers in Tanjung Karang (p > 0.05, r = 0.015) and Kelantan (p > 0.05, r = 0.0158). Besides, the frequency of BNu also has a positive correlation with the pesticide exposure among farmers in Tanjung Karang (p > 0.05, r = 0.036) and farmers in Kelantan (p > 0.05, r = 0.013). Hence, this present study demonstrated that exposure to pesticides increased the formation of MN and BNu among farmers and the prolonged use of pesticides may induce genotoxicity and DNA damage to human
    Matched MeSH terms: Cytogenetics
  16. Fulltext Microarray-Based Genomic Analysis Identifies Germline and Somatic Copy Number Variants and Loss of Heterozygosity in Acute Myeloid Leukaemia
    Ambayya, Angeli, Sasmita, Andrew Octavian, Zainina Seman, Chang, Kian Meng, Sathar, Jameela, Yegappan, Subramanian, et al.
    Malaysian Journal of Medicine and Health Sciences, 2018;14(103):1-14.
    MyJurnal
    Insights into molecular karyotyping using comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays enable the identification of copy number variations (CNVs) at a higher resolution and facilitate the detection of copy neutral loss of heterozygosity (CN-LOH) otherwise undetectable by conventional cytogenetics. The applicability of a customised CGH+SNP 180K DNA microarray in the diagnostic evaluation of Acute Myeloid Leukaemia (AML) in comparison with conventional karyotyping was assessed in this study. Methods: Paired tumour and germline post induction (remission sample obtained from the same patient after induction) DNA were used to delineate germline variants in 41 AML samples and compared with the karyotype findings. Results: After comparing the tumour versus germline DNA, a total of 55 imbalances (n 5-10 MB = 21, n 10-20 MB = 8 and n >20 MB = 26) were identified. Gains were most common in chromosome 4 (26.7%) whereas losses were most frequent in chromosome 7 (28.6%) and X (25.0%). CN-LOH was mostly seen in chromosome 4 (75.0%). Comparison between array CGH+SNP and karyotyping revealed 20 cases were in excellent agreement and 13 cases did not concord whereas in 15 cases finding could not be confirmed as no karyotypes available. Conclusion: The use of a combined array CGH+SNP in this study enabled the detection of somatic and germline CNVs and CN-LOHs in AML. Array CGH+SNP accurately determined chromosomal breakpoints compared to conventional cytogenetics in relation to presence of CNVs and CN-LOHs.
    Matched MeSH terms: Cytogenetics
  17. A Case Report of Concurrent IDH1 and NPM1 Mutations in a Novel t(X;2)(q28;p22) Translocation in Acute Myeloid Leukaemia without Maturation (AML-M1)
    Raveendran S, Sarojam S, Vijay S, Prem S, Sreedharan H
    Malays J Med Sci, 2015 Sep;22(5):93-97.
    PMID: 28239274
    Acute myeloid leukaemia (AML) is one of the fatal haematological malignancies as a consequence of its genetic heterogeneity. At present, the prediction of the clinical response to treatment for AML is based not only on detection of cytogenetic aberrations but also by analysing certain molecular genetic alterations. There are limited in sights into the contribution, disease progression, treatment outcome, and characterisation with respect to the uncommon chromosomal abnormalities leading to AML. Here, we describe the clinical, morphological, cytogenetic, and mutational findings of a 52-year-old female patient with AML without maturation (AML-M1). Conventional karyotyping and spectral karyotyping (SKY) were done on metaphase chromosomes from bone marrow cells at the time of diagnosis. A mutation analysis was performed on the hotspot regions of various genes, including FLT3, CEBPA, NPM1, RAS, c-KIT, IDH1 and IDH2. Cytogenetic and mutation analyses revealed a novel translocation, t(X;2)(q28;p22), with both NPM1 and IDH1 mutations. To the best of our knowledge, the presence of both NPM1 and IDH1 mutations in t(X;2)(q28;p22) is a novel finding in AML.
    Matched MeSH terms: Cytogenetics
  18. Fulltext Polymerase chain reaction analysis as a rapid screening test for diagnosis of fragile x syndrome
    Phan, CL, Zubaidah, Z., Gregory, A.R.A., Ten, SK, Kamariah, M.N., Thilagavathi, S., et al.
    Medicine & Health, 2006;1(1):36-44.
    MyJurnal
    Fragile X syndrome is a result of an unstable expansion of (CGG)n trinucleotide sequences in the FMR-1 (Fragile X Mental Retardation 1) gene site at Xq27. In a normal person, n ranges from 6 to 40 repeats with an average of 30 repeats, whereas in a mutated FMR1 gene the sequence is repeated several times over (stuttering gene). Full mutation occurs when n equals 200 repeats or more. Where n equals 50 to 200 repeats, it is a premutation. Fragile X occurs when the FMR-1 gene is unable to make normal amounts of usable Fragile X Mental Retardation Protein, or FMRP. The amount of FMRP in the body is one factor that determines the severity of the Fragile X syndrome. A person with nearly normal levels of FMRP usually has mild or no symptoms, while a person with very little or no normal FMRP has more severe symptoms. The mechanism for the role of the FMRP gene is still being researched upon. However, it has been observed that large numbers of repeats (more than 200) inactivates the gene through a process of methylation and when the gene is inactivated, the cell may make little or none of the needed FMRP. Inheritance is X-linked with reduced penetrance and the frequency of occurrence goes up through generations. The phenotypic manifestations of fragile-X syndrome vary and are largely dependent on the size of the mutation or premutation. The identification of the fragile site on G banded metaphases is a time consuming and delicate process requiring experience and skill, however, molecular diagnosis using DNA analysis and Southern blotting, even though expensive, is more specific in determining the presence or absence of the gene. This study was aimed to establish a rapid polymerase chain reaction (PCR) based - touch down PCR, as a screening method for fragile X syndrome. A total of six cases were analysed. Of these, one was a known case of Fragile X (T1) diagnosed by conventional cytogenetics, two were from the latter’s family members namely, his mother (T2) and father (T3), and the other two (T4 and T5) were randomly selected from patients presenting with dysmorphic features and delayed development respectively. One normal control (TC) was included. Cytogenetic analyses for detection of the fragile site was carried out in all cases. Two culture systems were used, namely the synchronised lymphocyte culture and the folate - thymidine deficient culture. Stained metaphases from the fragile X cultures were screened for the presence of the fragile site on the X chromosome. G-banded karyotyping was done using an image analyser to exclude presence of chromosomal abnormalities. DNA was extracted from these samples and amplified by touch-down PCR. Cytogenetic analysis revealed a folate-sensitive fragile site in the affected male, but none in the other five samples. G-banded karyotyping exhibited no additional chromosomal abnormalities. All extracted DNA samples were successfully amplified. Five of the samples showed presence of the product at the expected band at 552bp, excluding the presence of an expansion of CGG segment of the FMR-1 gene. The absence of a band in an affected individual, suggested a fully mutated allele of FRAXA (Folate Sensitive Fragile Site at Xq28). We succeeded in establishing a slightly modified touch-down PCR analysis. Our study indicates that PCR testing offers a rapid and specific method for screening of normal allele and full mutation of the fragile X gene. We suggest this technique to be applied as a complementary tool for cytogenetic analysis to detect the FRAXA gene.
    Matched MeSH terms: Cytogenetics
  19. Fulltext An update on imatinib mesylate therapy in chronic myeloid leukaemia patients in a teaching hospital in Malaysia
    Bee PC, Gan GG, Tai YT, Haris AR, Chin E, Veera SN
    Singapore Med J, 2012 Jan;53(1):57-61.
    PMID: 22252185
    The introduction of imatinib mesylate in 1998 has changed the management of chronic myeloid leukaemia. It is now the first-line therapy for newly diagnosed chronic myeloid leukaemia patients worldwide. However, its long-term survival benefit still needs to be established in clinical setting among Asian patients.
    Matched MeSH terms: Cytogenetics
  20. Fulltext Imatinib mesylate in the treatment of chronic myeloid leukemia: a local experience
    Bee PC, Gan GG, Teh A, Haris AR
    Med J Malaysia, 2006 Dec;61(5):547-52.
    PMID: 17623954 MyJurnal
    This study was done to assess the overall response rate of imatinib mesylate in local patients with chronic myeloid leukaemia. A total of 69 patients were recruited with male/female ratio of 7:3. Of the 69 patients; 35% were in the chronic phase, 41% were in the accelerated phase, 17% were in blast crisis and the remaining 7% were after stem cell transplantation. Complete haematological response rates of patients in chronic phase, accelerated phase and blast crisis were 95.8%, 96.4% and 41.7% respectively. Thirty-eight percent of patients achieved complete cytogenetic response and 10% achieved partial cytogenetic response. The cytogenetic response rates were 80%, 41.7% and 18.2% in chronic, accelerated and blast crisis phase respectively (p < 0.005). Twenty-six percent of patients developed anaemia, 13% had neutropenia and 12% had thrombocytopenia after starting on treatment. In addition, 14% of patients developed peripheral oedema, 13% complained of musculoskeletal pain, 12% had gastrointestinal side effects which include nausea, vomiting and diarrhoea, 9% had grade 1 hepatotoxicity, 7% developed skin rashes and one patient had an abnormal renal function test. Patients taking 600mg or higher dosage of imatinib had more gastrointestinal side effects. Patients who weighed less than 60kg had a much higher risk of developing anaemia. Anaemia was a negative predictor of cytogenetic response. Presenting high white blood cell counts and absence of cytogenetic response were also negative predictors of survival. Overall survival was 87%. This was affected by the different phases of disease (chronic phase was better than accelerated and blast crisis) (p < 0.001). In conclusion, our local CML patients did well on treatment with imatinib.
    Matched MeSH terms: Cytogenetics
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