MyMedR

Fulltext Analysis of sequence variations in low-density lipoprotein receptor gene among Malaysian patients with familial hypercholesterolemia

Al-Khateeb A, Zahri MK, Mohamed MS, Sasongko TH, Ibrahim S, Yusof Z, et al.

BMC Med Genet, 2011;12:40.

PMID: 21418584 DOI: 10.1186/1471-2350-12-40

Familial hypercholesterolemia is a genetic disorder mainly caused by defects in the low-density lipoprotein receptor gene. Few and limited analyses of familial hypercholesterolemia have been performed in Malaysia, and the underlying mutations therefore remain largely unknown.We studied a group of 154 unrelated FH patients from a northern area of Malaysia (Kelantan). The promoter region and exons 2-15 of the LDLR gene were screened by denaturing high-performance liquid chromatography to detect short deletions and nucleotide substitutions, and by multiplex ligation-dependent probe amplification to detect large rearrangements.

Evaluation of the Atlas Helicobacter pylori stool antigen test for diagnosis of infection in adult patients

Osman HA, Hasan H, Suppian R, Bahar N, Hussin NS, Rahim AA, et al.

Asian Pac J Cancer Prev, 2014;15(13):5245-7.

PMID: 25040982

BACKGROUND: Helicobacter pylori (H. pylori) is one of the most important causes of dyspepsia and gastric cancer and diagnosis can be made by invasive or non-invasive methods. The Atlas Helicobacter pylori antigen test is a new rapid non-invasive method which is simple to conduct. The aim of this study was to determine its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy.

MATERIALS AND METHODS: This prospective study was conducted between July 2012 and December 2013. Stool samples of 59 dyspeptic patients who underwent upper endoscopy were evaluated for H. pylori stool antigen.

RESULTS: From the 59 patients who participated in this study, there were 36 (61%) males and 23 (39%) females. H. pylori was diagnosed in 24 (40.7%) gastric biopsies, 22 (91.7 %) of these being positive for the Atlas H. pylori antigen test. The sensitivity, specificity, PPV, NPV and accuracy were 91.7%, 100%, 100%, 94.6% and 96.6% respectively.

CONCLUSIONS: The Atlas H. pylori antigen test is a new non-invasive method which is simple to perform and avails reliable results in a few minutes. Thus it can be the best option for the diagnosis of H. pylori infection due to its high sensitivity and specificity.

Fulltext Population genetic structure of peninsular Malaysia Malay sub-ethnic groups

Hatin WI, Nur-Shafawati AR, Zahri MK, Xu S, Jin L, Tan SG, et al.

PLoS One, 2011;6(4):e18312.

PMID: 21483678 DOI: 10.1371/journal.pone.0018312

Patterns of modern human population structure are helpful in understanding the history of human migration and admixture. We conducted a study on genetic structure of the Malay population in Malaysia, using 54,794 genome-wide single nucleotide polymorphism genotype data generated in four Malay sub-ethnic groups in peninsular Malaysia (Melayu Kelantan, Melayu Minang, Melayu Jawa and Melayu Bugis). To the best of our knowledge this is the first study conducted on these four Malay sub-ethnic groups and the analysis of genotype data of these four groups were compiled together with 11 other populations' genotype data from Indonesia, China, India, Africa and indigenous populations in Peninsular Malaysia obtained from the Pan-Asian SNP database. The phylogeny of populations showed that all of the four Malay sub-ethnic groups are separated into at least three different clusters. The Melayu Jawa, Melayu Bugis and Melayu Minang have a very close genetic relationship with Indonesian populations indicating a common ancestral history, while the Melayu Kelantan formed a distinct group on the tree indicating that they are genetically different from the other Malay sub-ethnic groups. We have detected genetic structuring among the Malay populations and this could possibly be accounted for by their different historical origins. Our results provide information of the genetic differentiation between these populations and a valuable insight into the origins of the Malay sub-ethnic groups in Peninsular Malaysia.

Chromosomal alterations in Malaysian patients with nasopharyngeal carcinoma analyzed by comparative genomic hybridization

Natasya Naili MN, Hasnita CH, Shamim AK, Hasnan J, Fauziah MI, Narazah MY, et al.

Cancer Genet. Cytogenet., 2010 Dec;203(2):309-12.

PMID: 21156250 DOI: 10.1016/j.cancergencyto.2010.07.136

Nasopharyngeal carcinoma (NPC) is one of the most common cancers in Malaysia, mainly occurring among the Chinese population. To detect common genetic alterations in NPC, we screened seven cases of NPC using the comparative genomic hybridization (CGH) technique. Before proceeding to the CGH technique, the tumors were first confirmed to consist of 75% tumor cells or more. In brief, the technique consists of binding tumor DNA with normal DNA and human Cot-1 DNA, which is then hybridized to normal metaphase spreads. The slides were then counterstained with 4,6 diamino-2-phenylindole (DAPI II) for detection. Analyses were performed using CGH software (Cytovision). We found genetic alterations in all seven NPC samples. The common chromosomal gains (57%, four cases) were found on chromosome arms 1q, 4p, 5, 7q, 11, 14p, 15q, 18p, and 21p, and common chromosomal losses (43%, three cases) were found on chromosome arm 16p. Our results showed chromosomal alterations in all seven NPC cases in the Malaysian population. This result provides the platform for further investigations to locate tumor suppressor genes and oncogenes at specific chromosomal regions in Malaysian NPC patients.

Fulltext Screening of dystrophin gene deletions in Malaysian patients with Duchenne muscular dystrophy

Marini M, Salmi AA, Watihayati MS, SMardziah MD, Zahri MK, Hoh BP, et al.

Med J Malaysia, 2008 Mar;63(1):31-4.

PMID: 18935728 MyJurnal

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive genetic disorder characterized by rapidly progressive muscle weakness. The disease is caused by deletion, duplication or point mutation of the dystrophin gene, located on the X chromosome (Xp21). Deletion accounts for 60% of the mutations within the 79 exons of the dystrophin gene. Seven exons (43, 44, 45, 46, 49, 50, and 51) were found to be most commonly deleted among the Asian patients. To detect the frequency of deletion of these 7 exons in Malaysian DMD patients, we carried out a molecular genetic analysis in 20 Malaysian DMD patients. The mean age of initial presentation was 60 months (SD 32 months, range 5-120 months). Fourteen patients were found to have deletion of at least one of the seven exons. The remaining six patients did not show any deletion on the tested exons. Deletions of exons 49, 50 and 51 were the most frequent (71.43%) and appear to be the hot spots in our cohort of patients.

A novel single nucleotide polymorphism, IVS2 -97A>T, in the prostaglandin F2alpha receptor gene was identified among the Malaysian patients with glaucoma

Peng HB, Zahary MN, Tajudin LS, Lin CL, Teck CM, Sidek MR, et al.

Kobe J Med Sci, 2007;53(1-2):49-52.

PMID: 17582204

The Prostaglandin F2alpha (PGF2alpha) receptor gene has been found to play an important role in reducing the intraocular pressure of the glaucomatous patients. Variations of the PGF2alpha receptor gene may be responsible for the differences in the response to an antiglaucoma drug, Latanoprost. A combined method of denaturing High Performance Liquid Chromatography (dHPLC) and sequencing was applied to detection of the PGF2alpha receptor gene variant among the 76 Malaysian patients with glaucoma, and a novel single nucleotide polymorphism (SNP), IVS -97A>T, was identified. According to the genotyping analysis, 36.8% of the subjects were heterozygous for the variant allele T, while 9.2% homozygous. The frequency of variant allele T was 0.28. Although with a limited number of samples, our data suggested that this polymorphism is common in the Malaysian patients with glaucoma.

Towards understanding the low prevalence of Helicobacter pylori in Malays: genetic variants among Helicobacter pylori-negative ethnic Malays in the north-eastern region of Peninsular Malaysia and Han Chinese and South Indians

Maran S, Lee YY, Xu SH, Raj MS, Abdul Majid N, Choo KE, et al.

J Dig Dis, 2013 Apr;14(4):196-202.

PMID: 23241512 DOI: 10.1111/1751-2980.12023

To identify gene polymorphisms that differ between Malays, Han Chinese and South Indians, and to identify candidate genes for the investigation of their role in protecting Malays from Helicobacter pylori (H. pylori) infection.

Mutation spectrum of dystrophin gene in malaysian patients with Duchenne/Becker muscular dystrophy

Rani AQ, Sasongko TH, Sulong S, Bunyan D, Salmi AR, Zilfalil BA, et al.

J. Neurogenet., 2013 Jun;27(1-2):11-5.

PMID: 23438214 DOI: 10.3109/01677063.2012.762580

We undertook the clinical feature examination and dystrophin analysis using multiplex ligation-dependent probe amplification (MLPA) and direct DNA sequencing of selected exons in a cohort of 35 Malaysian Duchenne/Becker muscular dystrophy (DMD/BMD) patients. We found 27 patients with deletions of one or more exons, 2 patients with one exon duplication, 2 patients with nucleotide deletion, and 4 patients with nonsense mutations (including 1 patient with two nonsense mutations in the same exon). Although most cases showed compliance to the reading frame rule, we found two unrelated DMD patients with an in-frame deletion of the gene. Two novel mutations have been detected in the Dystrophin gene and our results were compatible with other studies where the majority of the mutations (62.8%) are located in the distal hotspot. However, the frequency of the mutations in our patient varied as compared with those found in other populations.

Fulltext Harmonizing the interpretation of genetic variants across the world: the Malaysian experience

Hassan NN, Plazzer JP, Smith TD, Halim-Fikri H, Macrae F, Zubaidi AA, et al.

BMC Res Notes, 2016;9:125.

PMID: 26915360 DOI: 10.1186/s13104-015-1798-0

Databases for gene variants are very useful for sharing genetic data and to facilitate the understanding of the genetic basis of diseases. This report summarises the issues surrounding the development of the Malaysian Human Variome Project Country Node. The focus is on human germline variants. Somatic variants, mitochondrial variants and other types of genetic variation have corresponding databases which are not covered here, as they have specific issues that do not necessarily apply to germline variations.

A simple and rapid genotyping method for beta-2 receptor (beta2 AR) gene using allele specific multiplex PCR

Romaino SM, Teh LK, Zilfalil BA, Thong CP, Ismail AA, Amir J, et al.

J Clin Pharm Ther, 2004 Feb;29(1):47-52.

PMID: 14748897 DOI: 10.1046/j.1365-2710.2003.00535.x

Polymorphism of the beta2-adrenergic receptor (beta2 AR) gene is an important determinant of the function of this receptor. It affects receptor down-regulation and beta2-agonist responses. It has also been a focus of interest in attempts to elucidate the genetic basis of asthma, hypertension, obesity and cystic fibrosis. Several different techniques have been established to determine beta2 AR genotypes but none of these methods are simple enough to detect simultaneously all the five alleles of our research interest (Arg16/Gly16, -20T/C, Gln27/Glu27, -47T/C and Thr164/Ile164).

Transforming growth factor-alpha and nonsyndromic cleft lip with or without palate or cleft palate only in Kelantan, Malaysia

Rahman RA, Ahmad A, Rahman ZA, Mokhtar KI, Lah NA, Zilfalil BA, et al.

Cleft Palate Craniofac J, 2008 Nov;45(6):583-6.

PMID: 18956930 DOI: 10.1597/07-020.1

To determine the frequency of the transforming growth factor-alpha (TGFalpha) Taq1 polymorphism in nonsyndromic cleft lip with or without cleft palate (CL+/-P) and cleft palate only (CP) in Kelantan, Malaysia.

Fulltext Gastric precancerous lesions are associated with gene variants in Helicobacter pylori-susceptible ethnic Malays

Maran S, Lee YY, Xu S, Rajab NS, Hasan N, Syed Abdul Aziz SH, et al.

World J Gastroenterol, 2013 Jun 21;19(23):3615-22.

PMID: 23801863 DOI: 10.3748/wjg.v19.i23.3615

To identify genes associated with gastric precancerous lesions in Helicobacter pylori (H. pylori)-susceptible ethnic Malays.

Analysis of the genetic structure of the Malay population: Ancestry-informative marker SNPs in the Malay of Peninsular Malaysia

Yahya P, Sulong S, Harun A, Wan Isa H, Ab Rajab NS, Wangkumhang P, et al.

Forensic Sci Int Genet, 2017 09;30:152-159.

PMID: 28743033 DOI: 10.1016/j.fsigen.2017.07.005

Malay, the main ethnic group in Peninsular Malaysia, is represented by various sub-ethnic groups such as Melayu Banjar, Melayu Bugis, Melayu Champa, Melayu Java, Melayu Kedah Melayu Kelantan, Melayu Minang and Melayu Patani. Using data retrieved from the MyHVP (Malaysian Human Variome Project) database, a total of 135 individuals from these sub-ethnic groups were profiled using the Affymetrix GeneChip Mapping Xba 50-K single nucleotide polymorphism (SNP) array to identify SNPs that were ancestry-informative markers (AIMs) for Malays of Peninsular Malaysia. Prior to selecting the AIMs, the genetic structure of Malays was explored with reference to 11 other populations obtained from the Pan-Asian SNP Consortium database using principal component analysis (PCA) and ADMIXTURE. Iterative pruning principal component analysis (ipPCA) was further used to identify sub-groups of Malays. Subsequently, we constructed an AIMs panel for Malays using the informativeness for assignment (In) of genetic markers, and the K-nearest neighbor classifier (KNN) was used to teach the classification models. A model of 250 SNPs ranked by In, correctly classified Malay individuals with an accuracy of up to 90%. The identified panel of SNPs could be utilized as a panel of AIMs to ascertain the specific ancestry of Malays, which may be useful in disease association studies, biomedical research or forensic investigation purposes.

Fulltext Detection of beta-globin gene mutations among Kelantan Malay thalassaemia patients by polymerase chain reaction restriction fragment length polymorphism

Rozitah R, Nizam MZ, Nur Shafawati AR, Nor Atifah MA, Dewi M, Kannan TP, et al.

Singapore Med J, 2008 Dec;49(12):1046-9.

PMID: 19122960

Beta-thalassaemia major is an autosomal recessive disorder that results in severe microcytic, hypochromic, haemolytic anaemia among affected patients. Beta-thalassaemia has emerged as one of the most common public health problems in Malaysia, particularly among Malaysian Chinese and Malays. This study aimed to observe the spectrum of mutations found in Kelantan Malay beta-thalassaemia major patients who attended the Paediatrics Daycare Unit, Hospital Universiti Sains Malaysia, Kelantan, Malaysia, the data of which was being used in establishing the prenatal diagnosis in this Human Genome Centre.

Fulltext Cytogenetic and clinical profile of Down syndrome in Northeast Malaysia

Azman BZ, Ankathil R, Siti Mariam I, Suhaida MA, Norhashimah M, Tarmizi AB, et al.

Singapore Med J, 2007 Jun;48(6):550-4.

PMID: 17538755

This study was designed to evaluate the karyotype pattern, clinical features and other systemic anomalies of patients with Down syndrome in Malaysia.

Allele-specific PCR for a cost-effective & time-efficient diagnostic screening of spinal muscular atrophy

Marini M, Sasongko TH, Watihayati MS, Atif AB, Hayati F, Gunadi, et al.

Indian J Med Res, 2012;135:31-5.

PMID: 22382180

Genetic diagnosis of spinal muscular atrophy (SMA) is complicated by the presence of SMN2 gene as majority of SMA patients show absence or deletion of SMN1 gene. PCR may amplify both the genes non selectively in presence of high amount of DNA. We evaluated whether allele-specific PCR for diagnostic screening of SMA is reliable in the presence of high amount of genomic DNA, which is commonly used when performing diagnostic screening using restriction enzymes.

Obtaining assent for research involving children in Malaysia: a position statement from the Academy of Medicine of Malaysia College of Paediatrics

Khoo EJ, Zilfalil BA, Thong MK, Yong SC, Chee SC, Lee JK, et al.

Med J Malaysia, 2024 Jul;79(4):494-497.

PMID: 39086351

The Academy of Medicine of Malaysia College of Paediatrics acknowledges the role of children in research and this position statement explores the ethical considerations in obtaining assent from minors in the Malaysian context. It highlights the importance in respecting children's agency and navigating cultural complexities. The College proposes flexibility in the minimum age for assent of at least nine years old, while emphasising the need for a tailored assent procedure. Addressing language and cultural diversities and expanding local empirical research on a formal assent process are some building blocks in developing a standardised nationwide process in obtaining assent from children.

Fulltext A genome wide pattern of population structure and admixture in peninsular Malaysia Malays

Hatin WI, Nur-Shafawati AR, Etemad A, Jin W, Qin P, Xu S, et al.

Hugo J, 2014 Dec;8(1):5.

PMID: 27090253 DOI: 10.1186/s11568-014-0005-z

BACKGROUND: The Malays consist of various sub-ethnic groups which are believed to have different ancestral origins based on their migrations centuries ago. The sub-ethnic groups can be divided based on the region they inhabit; the northern (Melayu Kedah and Melayu Kelantan), western (Melayu Minang) and southern parts (Melayu Bugis and Melayu Jawa) of Peninsular Malaysia. We analyzed 54,794 autosomal single nucleotide polymorphisms (SNPs) which were shared by 472 unrelated individuals from 17 populations to determine the genetic structure and distributions of the ancestral genetic components in five Malay sub-ethnic groups namely Melayu Bugis, Melayu Jawa, Melayu Minang, Melayu Kedah, and Melayu Kelantan. We also have included in the analysis 12 other study populations from Thailand, Indonesia, China, India, Africa and Orang Asli sub-groups in Malay Peninsula, obtained from the Pan Asian SNP Initiative (PASNPI) Consortium and International HapMap project database.

RESULTS: We found evidence of genetic influx from Indians to Malays, more in Melayu Kedah and Melayu Kelantan which are genetically different from the other Malay sub-ethnic groups, but similar to Thai Pattani. More than 98% of these northern Malays haplotypes could be found in either Indians or Chinese populations, indicating a highly admixture pattern among populations. Nevertheless, the ancestry lines of Malays, Indonesians and Thais were traced back to have shared a common ancestor with the Proto-Malays and Chinese.

CONCLUSIONS: These results support genetic admixtures in the Peninsular Malaysia Malay populations and provided valuable information on the enigmatic demographical history as well as shed some insights into the origins of the Malays in the Malay Peninsula.

Novel complex re-arrangement of ARG1 commonly shared by unrelated patients with hyperargininemia

Mohseni J, Boon Hock C, Abdul Razak C, Othman SN, Hayati F, Peitee WO, et al.

Gene, 2014 Jan 1;533(1):240-5.

PMID: 24103480 DOI: 10.1016/j.gene.2013.09.081

Hyperargininemia is a very rare progressive neurometabolic disorder caused by deficiency of hepatic cytosolic arginase I, resulting from mutations in the ARG1 gene. Until now, some mutations were reported worldwide and none of them were of Southeast Asian origins. Furthermore, most reported mutations were point mutations and a few others deletions or insertions.

Two closely spaced nonsense mutations in the DMD gene in a Malaysian family

Rani AQ, Malueka RG, Sasongko TH, Awano H, Lee T, Yagi M, et al.

Mol Genet Metab, 2011 Jul;103(3):303-4.

PMID: 21514860 DOI: 10.1016/j.ymgme.2011.04.002

In Duchenne muscular dystrophy (DMD), identification of one nonsense mutation in the DMD gene has been considered an endpoint of genetic diagnosis. Here, we identified two closely spaced nonsense mutations in the DMD gene. In a Malaysian DMD patient two nonsense mutations (p.234S>X and p.249Q>X, respectively) were identified within exon 8. The proband's mother carried both mutations on one allele. Multiple mutations may explain the occasional discrepancies between genotype and phenotype in dystrophinopathy.

Displaying publications 41 - 60 of 81 in total