Displaying all 11 publications

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  1. Haslan, H., Zar Chi, T., Mohd Yusoff, Y.
    Medicine & Health, 2016;11(2):27-34.
    MyJurnal
    Fifth metatarsal bone fracture is one of the most commonest fractures of the foot.
    The decision for surgical or conservative approach is still inconclusive. Scoring
    system, decision analysis model and classification system are established to weigh
    between surgical and conservation approaches. Its unique anatomy and surgical
    complication influence decision on optimal surgical approach. Therefore, the
    present review attempts to look at factors that might influence decision making in
    management of fifth metatarsal fracture.
  2. Wan Hassan WN, Yusoff Y, Mardi NA
    Am J Orthod Dentofacial Orthop, 2017 Jan;151(1):209-218.
    PMID: 28024776 DOI: 10.1016/j.ajodo.2016.08.019
    INTRODUCTION: Rapid prototyping models can be reconstructed from stereolithographic digital study model data to produce hard-copy casts. In this study, we aimed to compare agreement and accuracy of measurements made with rapid prototyping and stone models for different degrees of crowding.

    METHODS: The Z Printer 450 (3D Systems, Rock Hill, SC) reprinted 10 sets of models for each category of crowding (mild, moderate, and severe) scanned using a structured-light scanner (Maestro 3D, AGE Solutions, Pisa, Italy). Stone and RP models were measured using digital calipers for tooth sizes in the mesiodistal, buccolingual, and crown height planes and for arch dimension measurements. Bland-Altman and paired t test analyses were used to assess agreement and accuracy. Clinical significance was set at ±0.50 mm.

    RESULTS: Bland-Altman analysis showed the mean bias of measurements between the models to be within ±0.15 mm (SD, ±0.40 mm), but the 95% limits of agreement exceeded the cutoff point of ±0.50 mm (lower range, -0.81 to -0.41 mm; upper range, 0.34 to 0.76 mm). Paired t tests showed statistically significant differences for all planes in all categories of crowding except for crown height in the moderate crowding group and arch dimensions in the mild and moderate crowding groups.

    CONCLUSIONS: The rapid prototyping models were not clinically comparable with conventional stone models regardless of the degree of crowding.

  3. Mat Yusoff Y, Ahid F, Abu Seman Z, Abdullah J, Kamaluddin NR, Esa E, et al.
    Mol Cytogenet, 2021 Sep 24;14(1):45.
    PMID: 34560908 DOI: 10.1186/s13039-021-00561-2
    BACKGROUND: Relapsed acute myeloid leukemia (AML) is associated with the acquisition of additional somatic mutations which are thought to drive phenotypic adaptability, clonal selection and evolution of leukemic clones during treatment. We performed high throughput exome sequencing of matched presentation and relapsed samples from 6 cytogenetically normal AML (CN-AML) patients treated with standard remission induction chemotherapy in order to contribute with the investigation of the mutational landscape of CN-AML and clonal evolution during AML treatment.

    RESULT: A total of 24 and 32 somatic variants were identified in presentation and relapse samples respectively with an average of 4.0 variants per patient at presentation and 5.3 variants per patient at relapse, with SNVs being more frequent than indels at both disease stages. All patients have somatic variants in at least one gene that is frequently mutated in AML at both disease presentation and relapse, with most of these variants are classic AML and recurrent hotspot mutations including NPM1 p.W288fs, FLT3-ITD, NRAS p.G12D and IDH2 p.R140Q. In addition, we found two distinct clonal evolution patterns of relapse: (1) a leukemic clone at disease presentation acquires additional mutations and evolves into the relapse clone after the chemotherapy; (2) a leukemic clone at disease presentation persists at relapse without the addition of novel somatic mutations.

    CONCLUSIONS: The findings of this study suggest that the relapse-initiating clones may pre-exist prior to therapy, which harbor or acquire mutations that confer selective advantage during chemotherapy, resulting in clonal expansion and eventually leading to relapse.

  4. Yasin NM, Abdul Hamid FS, Hassan S, Mat Yusoff Y, Mohd Sahid EN, Esa E
    Diagnostics (Basel), 2023 Oct 23;13(20).
    PMID: 37892108 DOI: 10.3390/diagnostics13203286
    Malaysia is a multicultural and multiethnic country comprising numerous ethnic groups. From the total population of 32.7 million, Malays form the bulk of the Bumiputera in Malaysia comprise about 69.9%, followed by Chinese 22.8%, Indian 6.6%, and others 0.7%. The heterogeneous population and increasing numbers of non-citizens in this country affects the heterogeneity of genetic diseases, diversity, and heterogeneity of thalassaemia mutations. Alpha (α)-thalassaemia is an inherited haemoglobin disorder characterized by hypochromic microcytic anaemia caused by a quantitative reduction in the α-globin chain. A majority of the α-thalassaemia are caused by deletions in the α-globin gene cluster. Among Malays, the most common deletional alpha thalassaemia is -α3.7 deletion followed by --SEA deletion. We described the molecular characterization of a new --GB deletion in our population, involving both alpha genes in cis. Interestingly, we found that this mutation is unique among Malay ethnicities. It is important to diagnose this deletion because of the 25% risk of Hb Bart's with hydrops fetalis in the offspring when in combination with another α0- thalassaemia allele. MLPA is a suitable method to detect unknown and uncommon deletions and to characterize those cases which remain unresolved after a standard diagnostic approach.
  5. Mat Yusoff Y, Abu Seman Z, Othman N, Kamaluddin NR, Esa E, Zulkiply NA, et al.
    Asian Pac J Cancer Prev, 2018 Dec 25;19(12):3317-3320.
    PMID: 30583336
    Objective: Chronic Myeloid Leukemia (CML) is caused by a reciprocal translocation between chromosomes 9
    and 22, t(9;22) (q34;q11) which encodes for the BCR-ABL fusion protein. Discovery of Imatinib Mesylate (IM) as
    first line therapy has brought tremendous improvement in the management of CML. However, emergence of point
    mutations within the BCR-ABL gene particularly T315I mutation, affects a common BCR-ABL kinase contact residue
    which impairs drug binding thus contribute to treatment resistance. This study aims to investigate the BCR-ABL T315I
    mutation in Malaysian patients with CML. Methods: A total of 285 patients diagnosed with CML were included in this
    study. Mutation detection was performed using qualitative real-time PCR (qPCR). Results: Fifteen out of 285 samples
    (5.26%) were positive for T315I mutations after amplification with real-time PCR assay. From the total number of
    positive samples, six patients were in accelerated phase (AP), four in chronic phase (CP) and five in blast crisis (BC).
    Conclusion: Mutation testing is recommended for choosing various tyrosine kinase inhibitors (TKIs) to optimize
    outcomes for both cases of treatment failure or suboptimal response to imatinib. Therefore, detection of T315I mutation
    in CML patients are clinically useful in the selection of appropriate treatment strategies to prevent disease progression.
  6. Mat Yusoff Y, Abu Seman Z, Othman N, Kamaluddin NR, Esa E, Zulkiply NA, et al.
    Asian Pac J Cancer Prev, 2019 06 01;20(6):1749-1755.
    PMID: 31244296 DOI: 10.31557/APJCP.2019.20.6.1749
    Objective: The most frequent acquired molecular abnormalities and important prognostic indicators in patients
    with Acute Myeloid Leukaemia (AML) are fms-like tyrosine kinase-3 gene (FLT3) and nucleophosmin-1 (NPM1)
    mutations. Our study aims to develop a cost effective and comprehensive in-house conventional PCR method for
    detection of FLT3-ITD, FLT3-D835 and NPM1 mutations and to evaluate the frequency of these mutations in patients
    with cytogenetically normal (CN) AML in our population. Methods: A total of 199 samples from AML patients (95
    women, 104 men) were included in the study. Mutation analyses were performed using polymerase chain reaction
    (PCR) and gene sequencing. Result: Sixty-eight patients were positive for the mutations. FLT3-ITD mutations were
    detected in 32 patients (16.1%), followed by FLT3-D835 in 5 (2.5%) and NPM1 in 54 (27.1%). Double mutations of
    NPM1 and FLT3-ITD were detected in 23 cases (11.6%). Assays validation were performed using Sanger sequencing
    and showed 100% concordance with in house method. Conclusion: The optimized in-house PCR assays for the
    detection of FLT3-ITD, FLT3-D835 and NPM1 mutations in AML patients were robust, less labour intensive and cost
    effective. These assays can be used as diagnostic tools for mutation detection in AML patients since identification of
    these mutations are important for prognostication and optimization of patient care.
  7. Zakaria Z, Othman N, Ismail A, Kamaluddin NR, Esa E, Abdul Rahman EJ, et al.
    Asian Pac J Cancer Prev, 2017 04 01;18(4):1169-1175.
    PMID: 28548470
    Background: ETV6/RUNX1 gene fusion is the most frequently seen chromosomal abnormality in childhood acute
    lymphobastic leukamia (ALL). However, additional genetic changes are known to be required for the development of
    this type of leukaemia. Therefore, we here aimed to assess the somatic mutational profile of four ALL cases carrying the
    ETV6/RUNX1 fusion gene using whole-exome sequencing. Methods: DNA was isolated from bone marrow samples
    using a QIAmp DNA Blood Mini kit and subsequently sequenced using the Illumina MiSeq system. Results: We
    identified 12,960 to17,601 mutations in each sample, with a total of 16,466 somatic mutations in total. Some 15,533
    variants were single nucleotide polymorphisms (SNPs), 129 were substitutions, 415 were insertions and 389 were
    deletions. When taking into account the coding region and protein impact, 1,875 variants were synonymous and 1,956
    were non-synonymous SNPs. Among non-synonymous SNPs, 1,862 were missense, 13 nonsense, 35 frameshifts, 11
    nonstop, 3 misstart, 15 splices disrupt and 17 in-frame indels. A total of 86 variants were located in leukaemia-related
    genes of which 32 variants were located in the coding regions of GLI2, SP140, GATA2, SMAD5, KMT2C, CDH17,
    CDX2, FLT3, PML and MOV10L1. Conclusions: Detection and identification of secondary genetic alterations are
    important in identifying new therapeutic targets and developing rationally designed treatment regimens with less
    toxicity in ALL patients.
  8. Yasin NM, Abdul Hamid FS, Hassan S, Sudin A, Yassim H, Mohd Sahid EN, et al.
    Front Pediatr, 2022;10:974496.
    PMID: 36533237 DOI: 10.3389/fped.2022.974496
    ABSTRACT: We report the haematological parameters and molecular characterization of beta zero (β°) South East Asia (SEA) deletion in the HBB gene cluster with unusually high levels of Hb F compared to a classical heterozygous beta zero (β°)-thalassaemia.

    METHODS: Retrospective study on 17 cases of (β°) South East Asia (SEA) deletion from 2016 to 2019 referred to Institute for Medical Research were conducted. The clinical information and haematological profiles were evaluated. The mutation was analyzed, and the results were compared with other β°-thalassaemia groups. For HBB gene genotyping, all the cases were subjected for multiplex gap-PCR, 5 cases were subjected for HBB gene sequencing for exclusion of compound heterozygous with other beta variants. Co-inheritance of α-thalassaemia were determined using multiplex gap-PCR and multiplex ARMS-PCR.

    RESULTS: Seventeen cases were positive for β°-thal SEA deletion. Fifteen cases were heterozygous and two were compound heterozygous for β°-thal SEA deletion. The results were compared with 182 cases of various heterozygous β° deletions and mutations. The mean Hb for heterozygous β°-thal SEA deletion (13.44 ± 1.45 g/dl) was normal and significantly higher than heterozygous IVS 1-1 and Codon 41/42 (post hoc test, p 

  9. Esa E, Hashim AK, Mohamed EHM, Zakaria Z, Abu Hassan AN, Mat Yusoff Y, et al.
    Genet Test Mol Biomarkers, 2021 Mar;25(3):199-210.
    PMID: 33734890 DOI: 10.1089/gtmb.2020.0182
    Background: The association between dysregulated microRNAs (miRNAs) and acute myeloid leukemia (AML) is well known. However, our understanding of the regulatory role of miRNAs in the cytogenetically normal AML (CN-AML) subtype pathway is still poor. The current study integrated miRNA and mRNA profiles to explore novel miRNA-mRNA interactions that affect the regulatory patterns of de novo CN-AML. Methods: We utilized a multiplexed nanoString nCounter platform to profile both miRNAs and mRNAs using similar sets of patient samples (n = 24). Correlations were assessed, and an miRNA-mRNA network was constructed. The underlying biological functions of the mRNAs were predicted by gene enrichment. Finally, the interacting pairs were assessed using TargetScan and microT-CDS. We identified 637 significant negative correlations (false discovery rate <0.05). Results: Network analysis revealed a cluster of 12 miRNAs representing the majority of mRNA targets. Within the cluster, five miRNAs (miR-495-3p, miR-185-5p, let-7i-5p, miR-409-3p, and miR-127-3p) were posited to play a pivotal role in the regulation of CN-AML, as they are associated with the negative regulation of myeloid leukocyte differentiation, negative regulation of myeloid cell differentiation, and positive regulation of hematopoiesis. Conclusion: Three novel interactions in CN-AML were predicted as let-7i-5p:HOXA9, miR-495-3p:PIK3R1, and miR-495-3p:CDK6 may be responsible for regulating myeloid cell differentiation in CN-AML.
  10. Chowdhury R, Noh MFM, Ismail SR, van Daalen KR, Kamaruddin PSNM, Zulkiply SH, et al.
    JMIR Res Protoc, 2022 Feb 10;11(2):e31885.
    PMID: 35142634 DOI: 10.2196/31885
    BACKGROUND: Although the burden of premature myocardial infarction (MI) is high in Malaysia, direct evidence on the determinants of MI in this multi-ethnic population remains sparse.

    OBJECTIVE: The Malaysian Acute Vascular Events Risk (MAVERIK) study is a retrospective case-control study established to investigate the genomic, lipid-related, and other determinants of acute MI in Malaysia. In this paper, we report the study protocol and early results.

    METHODS: By June 2019, we had enrolled approximately 2500 patients with their first MI and 2500 controls without cardiovascular disease, who were frequency-matched by age, sex, and ethnicity, from 17 hospitals in Malaysia. For each participant, serum and whole blood have been collected and stored. Clinical, demographic, and behavioral information has been obtained using a 200-item questionnaire.

    RESULTS: Tobacco consumption, a history of diabetes, hypertension, markers of visceral adiposity, indicators of lower socioeconomic status, and a family history of coronary disease were more prevalent in cases than in controls. Adjusted (age and sex) logistic regression models for traditional risk factors indicated that current smoking (odds ratio [OR] 4.11, 95% CI 3.56-4.75; P30 kg/m2; OR 1.19, 95% CI 1.05-1.34; P=.009) were associated with MI in age- and sex-adjusted models.

    CONCLUSIONS: The MAVERIK study can serve as a useful platform to investigate genetic and other risk factors for MI in an understudied Southeast Asian population. It should help to hasten the discovery of disease-causing pathways and inform regionally appropriate strategies that optimize public health action.

    INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/31885.

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