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  1. Price D, David-Wang A, Cho SH, Ho JC, Jeong JW, Liam CK, et al.
    J Asthma, 2016 09;53(7):761-9.
    PMID: 27096388 DOI: 10.3109/02770903.2016.1141951
    OBJECTIVE: We examined the physician perspectives on asthma management in Asia.

    METHODS: An online/face-to-face, questionnaire-based survey of respiratory specialists and primary care physicians from eight Asian countries/region was carried out. The survey explored asthma control, inhaler selection, technique and use; physician-patient communications and asthma education. Inclusion criteria were >50% of practice time spent on direct patient care; and treated >30 patients with asthma per month, of which >60% were aged >12 years.

    RESULTS: REALISE Asia (Phase 2) involved 375 physicians with average 15.9(±6.8) years of clinical experience. 89.1% of physicians reporting use of guidelines estimated that 53.2% of their patients have well-controlled (GINA-defined) asthma. Top consideration for inhaler choice was asthma severity (82.4%) and lowest, socio-economic status (32.5%). Then 54.7% of physicians checked their patients' inhaler techniques during consultations but 28.2(±19.1)% of patients were using their inhalers incorrectly; 21.1-57.9% of physicians could spot improper inhaler techniques in video demonstrations. And 79.6% of physicians believed combination inhalers could increase adherence because of convenience (53.7%), efficacy (52.7%) and usability (18.9%). Initial and follow-up consultations took 16.8(±8.4) and 9.2(±5.3) minutes, respectively. Most (85.1%) physicians used verbal conversations and least (24.5%), video demonstrations of inhaler use; 56.8% agreed that patient attitudes influenced their treatment approach.

    CONCLUSION: Physicians and patients have different views of 'well-controlled' asthma. Although physicians informed patients about asthma and inhaler usage, they overestimated actual usage and patients' knowledge was sub-optimal. Physician-patient interactions can be augmented with understanding of patient attitudes, visual aids and ancillary support to perform physical demonstrations to improve treatment outcomes.

  2. Boo L, Ho WY, Ali NM, Yeap SK, Ky H, Chan KG, et al.
    Int J Biol Sci, 2016;12(4):427-45.
    PMID: 27019627 DOI: 10.7150/ijbs.12777
    Breast cancer is the second leading cause of cancer-related mortality worldwide as most patients often suffer cancer relapse. The reason is often attributed to the presence of cancer stem cells (CSCs). Recent studies revealed that dysregulation of microRNA (miRNA) are closely linked to breast cancer recurrence and metastasis. However, no specific study has comprehensively characterised the CSC characteristic and miRNA transcriptome in spheroid-enriched breast cells. This study described the generation of spheroid MCF-7 cell in serum-free condition and the comprehensive characterisation for their CSC properties. Subsequently, miRNA expression differences between the spheroid-enriched CSC cells and their parental cells were evaluated using next generation sequencing (NGS). Our results showed that the MCF-7 spheroid cells were enriched with CSCs properties, indicated by the ability to self-renew, increased expression of CSCs markers, and increased resistance to chemotherapeutic drugs. Additionally, spheroid-enriched CSCs possessed greater cell proliferation, migration, invasion, and wound healing ability. A total of 134 significantly (p<0.05) differentially expressed miRNAs were identified between spheroids and parental cells using miRNA-NGS. MiRNA-NGS analysis revealed 25 up-regulated and 109 down-regulated miRNAs which includes some miRNAs previously reported in the regulation of breast CSCs. A number of miRNAs (miR-4492, miR-4532, miR-381, miR-4508, miR-4448, miR-1296, and miR-365a) which have not been previously reported in breast cancer were found to show potential association with breast cancer chemoresistance and self-renewal capability. The gene ontology (GO) analysis showed that the predicted genes were enriched in the regulation of metabolic processes, gene expression, DNA binding, and hormone receptor binding. The corresponding pathway analyses inferred from the GO results were closely related to the function of signalling pathway, self-renewability, chemoresistance, tumorigenesis, cytoskeletal proteins, and metastasis in breast cancer. Based on these results, we proposed that certain miRNAs identified in this study could be used as new potential biomarkers for breast cancer stem cell diagnosis and targeted therapy.
  3. Zheng W, Mutha NV, Heydari H, Dutta A, Siow CC, Jakubovics NS, et al.
    PeerJ, 2016;4:e1698.
    PMID: 27017950 DOI: 10.7717/peerj.1698
    Background. The gram-negative Neisseria is associated with two of the most potent human epidemic diseases: meningococcal meningitis and gonorrhoea. In both cases, disease is caused by bacteria colonizing human mucosal membrane surfaces. Overall, the genus shows great diversity and genetic variation mainly due to its ability to acquire and incorporate genetic material from a diverse range of sources through horizontal gene transfer. Although a number of databases exist for the Neisseria genomes, they are mostly focused on the pathogenic species. In this present study we present the freely available NeisseriaBase, a database dedicated to the genus Neisseria encompassing the complete and draft genomes of 15 pathogenic and commensal Neisseria species. Methods. The genomic data were retrieved from National Center for Biotechnology Information (NCBI) and annotated using the RAST server which were then stored into the MySQL database. The protein-coding genes were further analyzed to obtain information such as calculation of GC content (%), predicted hydrophobicity and molecular weight (Da) using in-house Perl scripts. The web application was developed following the secure four-tier web application architecture: (1) client workstation, (2) web server, (3) application server, and (4) database server. The web interface was constructed using PHP, JavaScript, jQuery, AJAX and CSS, utilizing the model-view-controller (MVC) framework. The in-house developed bioinformatics tools implemented in NeisseraBase were developed using Python, Perl, BioPerl and R languages. Results. Currently, NeisseriaBase houses 603,500 Coding Sequences (CDSs), 16,071 RNAs and 13,119 tRNA genes from 227 Neisseria genomes. The database is equipped with interactive web interfaces. Incorporation of the JBrowse genome browser in the database enables fast and smooth browsing of Neisseria genomes. NeisseriaBase includes the standard BLAST program to facilitate homology searching, and for Virulence Factor Database (VFDB) specific homology searches, the VFDB BLAST is also incorporated into the database. In addition, NeisseriaBase is equipped with in-house designed tools such as the Pairwise Genome Comparison tool (PGC) for comparative genomic analysis and the Pathogenomics Profiling Tool (PathoProT) for the comparative pathogenomics analysis of Neisseria strains. Discussion. This user-friendly database not only provides access to a host of genomic resources on Neisseria but also enables high-quality comparative genome analysis, which is crucial for the expanding scientific community interested in Neisseria research. This database is freely available at http://neisseria.um.edu.my.
  4. Yeow TC, Wong WF, Sabet NS, Sulaiman S, Shahhosseini F, Tan GM, et al.
    BMC Microbiol, 2016 Mar 18;16:45.
    PMID: 26987367 DOI: 10.1186/s12866-016-0671-1
    BACKGROUND: The 7.5 kb cryptic plasmid of Chlamydia trachomatis has been shown to be a virulence factor in animal models, but its significance in humans still remains unknown. The aim of this study was to investigate the prevalence and potential involvement of the C. trachomatis cryptic plasmid in causing various clinical manifestations; including infertility, reproductive tract disintegrity, menstrual disorder, and polycystic ovarian syndrome (PCOS) among genital C. trachomatis-infected patients.
    RESULTS:A tot l of 180 female patients of child bearing age (mean 30.9 years old, IQR:27-35) with gynecological complications and subfertility issues, who visited Obstetrics and Gynecology clinics in Kuala Lumpur, Malaysia were recruited for the study. Prevalence of genital chlamydial infection among these patients was alarmingly high at 51.1% (92/180). Of the 92 chlamydia-infected patients, 93.5% (86/92) were infected with plasmid-bearing (+) C. trachomatis while the remaining 6.5% (6/92) were caused by the plasmid-free (-) variant. Our data showed that genital C. trachomatis infection was associated with infertility issues, inflammation in the reproductive tract (mucopurulent cervicitis or endometriosis), irregular menstrual cycles and polycystic ovarian syndrome (PCOS). However, no statistical significance was detected among patients with plasmid (+) versus plasmid (-) C. trachomatis infection. Interestingly, plasmid (+) C. trachomatis was detected in all patients with PCOS, and the plasmid copy numbers were significantly higher among PCOS patients, relative to non-PCOS patients.
    CONCLUSION: Our findings show a high incidence of C. trachomatis infection among women with infertility or gynecological problems in Malaysia. However, due to the low number of plasmid (-) C. trachomatis cases, a significant role of the plasmid in causing virulence in human requires further investigation of a larger cohort.
    KEYWORDS: Chlamydia trachomatis; Infertility; Plasmid; Reproductive system disorders
    Study site: Obstetrics and Gynecology clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
  5. Jean SS, Coombs G, Ling T, Balaji V, Rodrigues C, Mikamo H, et al.
    Int J Antimicrob Agents, 2016 Apr;47(4):328-34.
    PMID: 27005459 DOI: 10.1016/j.ijantimicag.2016.01.008
    A total of 9599 isolates of Gram-negative bacteria (GNB) causing urinary tract infections (UTIs) were collected from 60 centres in 13 countries in the Asia-Pacific region from 2010-2013. These isolates comprised Enterobacteriaceae species (mainly Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Klebsiella oxytoca, Enterobacter cloacae and Morganella morganii) and non-fermentative GNB species (predominantly Pseudomonas aeruginosa and Acinetobacter baumannii). In vitro susceptibilities were determined by the agar dilution method and susceptibility profiles were determined using the minimum inhibitory concentration (MIC) interpretive breakpoints recommended by the Clinical and Laboratory Standards Institute in 2015. Production of extended-spectrum β-lactamases (ESBLs) amongst E. coli, K. pneumoniae, P. mirabilis and K. oxytoca isolates was determined by the double-disk synergy test. China, Vietnam, India, Thailand and the Philippines had the highest rates of GNB species producing ESBLs and the highest rates of cephalosporin resistance. ESBL production and hospital-acquired infection (isolates obtained ≥48h after admission) significantly compromised the susceptibility of isolates of E. coli and K. pneumoniae to ciprofloxacin, levofloxacin and most β-lactams, with the exception of imipenem and ertapenem. However, >87% of ESBL-producing E. coli strains were susceptible to amikacin and piperacillin/tazobactam, indicating that these antibiotics might be appropriate alternatives for treating UTIs due to ESBL-producing E. coli. Fluoroquinolones were shown to be inappropriate as empirical therapy for UTIs. Antibiotic resistance is a serious problem in the Asia-Pacific region. Therefore, continuous monitoring of evolutionary trends in the susceptibility profiles of GNB causing UTIs in Asia is crucial.
  6. Khosravi Y, Bunte RM, Chiow KH, Tan TL, Wong WY, Poh QH, et al.
    Gut Microbes, 2016;7(1):48-53.
    PMID: 26939851 DOI: 10.1080/19490976.2015.1119990
    Helicobacter pylori have been shown to influence physiological regulation of metabolic hormones involved in food intake, energy expenditure and body mass. It has been proposed that inducing H. pylori-induced gastric atrophy damages hormone-producing endocrine cells localized in gastric mucosal layers and therefore alter their concentrations. In a recent study, we provided additional proof in mice under controlled conditions that H. pylori and gut microbiota indeed affects circulating metabolic gut hormones and energy homeostasis. In this addendum, we presented data from follow-up investigations that demonstrated H. pylori and gut microbiota-associated modulation of metabolic gut hormones was independent and precedes H. pylori-induced histopathological changes in the gut of H. pylori-infected mice. Thus, H. pylori-associated argumentation of energy homeostasis is not caused by injury to endocrine cells in gastric mucosa.
  7. Abu Hassan MR, Ismail I, Mohd Suan MA, Ahmad F, Wan Khazim WK, Othman Z, et al.
    Epidemiol Health, 2016;38:e2016007.
    PMID: 26971697 DOI: 10.4178/epih.e2016007
    OBJECTIVES: This is the first study that estimates the incidence and mortality rate for colorectal cancer (CRC) patients in Malaysia by sex and ethnicity.

    METHODS: The 4,501 patients were selected from National Cancer Patient Registry-Colorectal Cancer data. Patient survival status was cross-checked with the National Registration Department. The age-standardised rate (ASR) was calculated as the proportion of CRC cases (incidence) and deaths (mortality) from 2008 to 2013, weighted by the age structure of the population, as determined by the Department of Statistics Malaysia and the World Health Organization world standard population distribution.

    RESULTS: The overall incidence rate for CRC was 21.32 cases per 100,000. Those of Chinese ethnicity had the highest CRC incidence (27.35), followed by the Malay (18.95), and Indian (17.55) ethnicities. The ASR incidence rate of CRC was 1.33 times higher among males than females (24.16 and 18.14 per 100,000, respectively). The 2011 (44.7%) CRC deaths were recorded. The overall ASR of mortality was 9.79 cases, with 11.85 among the Chinese, followed by 9.56 among the Malays and 7.08 among the Indians. The ASR of mortality was 1.42 times higher among males (11.46) than females (8.05).

    CONCLUSIONS: CRC incidence and mortality is higher in males than females. Individuals of Chinese ethnicity have the highest incidence of CRC, followed by the Malay and Indian ethnicities. The same trends were observed for the age-standardised mortality rate.

  8. Aydın Tekdaş D, Viswanathan G, Zehra Topal S, Looi CY, Wong WF, Min Yi Tan G, et al.
    Org Biomol Chem, 2016 Mar 7;14(9):2665-70.
    PMID: 26831779 DOI: 10.1039/c5ob02477c
    A novel BODIPY derivative was designed for biomedical applications. Its mono-quaternized structure ensured its water-solubility and suitable amphiphilicity. Showing no singlet oxygen generation to avoid damage to healthy cells, this new derivative proved to be an extremely promising antimicrobial agent, with activity equal or superior to ampicillin against MRS Staphylococcus strains with no short-term resistance issue. Its activity against MSS Staphylococcus strains was largely superior to those of ampicillin and reached the activity of vancomycin against MSS S. epidermidis. This latter result is in particular extremely promising for the treatment of hospital-acquired infections. Also the fluorescence properties of BODIPY allowed imaging of the uptake.
  9. Jan Mohamed HJ, Loy SL, Mohd Taib MN, Karim NA, Tan SY, Appukutty M, et al.
    BMC Public Health, 2015;15:1322.
    PMID: 26718818 DOI: 10.1186/s12889-015-2666-5
    The consumption of beverages contributes to diet quality and overall nutrition. Studies on malted drinks, one of the widely consumed beverage choices among children in Asia, however, have received limited attention. This study aimed to examine the prevalence of malted drink consumption and explored associations of sociodemographic characteristics, nutrient intakes, weight status and physical activity levels with malted drink consumption among primary school children in Malaysia.
  10. Chan KG, Loke MF, Ong BL, Wong YL, Hong KW, Tan KH, et al.
    PeerJ, 2015;3:e1367.
    PMID: 26587340 DOI: 10.7717/peerj.1367
    Background. Two non-tuberculous mycobacterial strains, UM_3 and UM_11, were isolated from the trunk wash of captive elephants in Malaysia. As they appeared to be identical phenotypes, they were investigated further by conventional and whole genome sequence-based methods of strain differentiation. Methods. Multiphasic investigations on the isolates included species identification with hsp65 PCR-sequencing, conventional biochemical tests, rapid biochemical profiling using API strips and the Biolog Phenotype Microarray analysis, protein profiling with liquid chromatography-mass spectrometry, repetitive sequence-based PCR typing and whole genome sequencing followed by phylogenomic analyses. Results. The isolates were shown to be possibly novel slow-growing schotochromogens with highly similar biological and genotypic characteristics. Both strains have a genome size of 5.2 Mbp, G+C content of 68.8%, one rRNA operon and 52 tRNAs each. They qualified for classification into the same species with their average nucleotide identity of 99.98% and tetranucleotide correlation coefficient of 0.99999. At the subspecies level, both strains showed 98.8% band similarity in the Diversilab automated repetitive sequence-based PCR typing system, 96.2% similarity in protein profiles obtained by liquid chromatography mass spectrometry, and a genomic distance that is close to zero in the phylogenomic tree constructed with conserved orthologs. Detailed epidemiological tracking revealed that the elephants shared a common habitat eight years apart, thus, strengthening the possibility of a clonal relationship between the two strains.
  11. Bhoo-Pathy N, Verkooijen HM, Tan EY, Miao H, Taib NA, Brand JS, et al.
    Sci Rep, 2015;5:16252.
    PMID: 26536962 DOI: 10.1038/srep16252
    Up to 25% of breast cancer patients in Asia present with de novo metastatic disease. We examined the survival trends of Asian patients with metastatic breast cancer over fifteen years. The impact of changes in patient's demography, tumor characteristics, tumor burden, and treatment on survival trend were examined. Patients with de novo metastatic breast cancer from three hospitals in Malaysia and Singapore (N = 856) were grouped by year of diagnosis: 1996-2000, 2001-2005 and 2006-2010. Step-wise multivariable Poisson regression was used to estimate the contribution of above-mentioned factors on the survival trend. Proportions of patients presenting with metastatic breast cancer were 10% in 1996-2000, 7% in 2001-2005, and 9% in 2006-2010. Patients in 2006-2010 were significantly older, appeared to have higher disease burden, and received more chemotherapy, endocrine therapy, and surgery of primary tumor. The three-year relative survival in the above periods were 20·6% (95% CI: 13·9%-28·2%), 28·8% (95% CI: 23·4%-34·2%), and 33·6% (95% CI: 28·8%-38·5%), respectively. Adjustment for treatment considerably attenuated the relative excess risk of mortality in recent years, compared to other factors. Substantial improvements in survival were observed in patients with de novo metastatic breast cancer in this study.
  12. Ak N, Koo HC, Hamid Jan JM, Mohd Nasir MT, Tan SY, Appukutty M, et al.
    PLoS One, 2015;10(10):e0138247.
    PMID: 26473369 DOI: 10.1371/journal.pone.0138247
    Diets rich in whole grain are associated with several health benefits. Little is known however, about whole grain consumption patterns in Malaysia. The aim of this study was to assess whole grain intakes and dietary source in Malaysian children and adolescents.
  13. Tan KL, Ling KH, Hewitt CA, Cheah PS, Simpson K, Gordon L, et al.
    Genom Data, 2014 Dec;2:314-7.
    PMID: 26484118 DOI: 10.1016/j.gdata.2014.09.009
    The Ts1Cje mouse model of Down syndrome (DS) has partial trisomy of mouse chromosome 16 (MMU16), which is syntenic to human chromosome 21 (HSA21). It develops various neuropathological features demonstrated by DS patients such as reduced cerebellar volume [1] and altered hippocampus-dependent learning and memory [2,3]. To understand the global gene expression effect of the partially triplicated MMU16 segment on mouse brain development, we performed the spatiotemporal transcriptome analysis of Ts1Cje and disomic control cerebral cortex, cerebellum and hippocampus harvested at four developmental time-points: postnatal day (P)1, P15, P30 and P84. Here, we provide a detailed description of the experimental and analysis procedures of the microarray dataset, which has been deposited in the Gene Expression Omnibus (GSE49050) database.
  14. Price D, David-Wang A, Cho SH, Ho JC, Jeong JW, Liam CK, et al.
    J Asthma Allergy, 2015;8:93-103.
    PMID: 26445555 DOI: 10.2147/JAA.S82633
    PURPOSE: Asthma is a global health problem, and asthma prevalence in Asia is increasing. The REcognise Asthma and LInk to Symptoms and Experience Asia study assessed patients' perception of asthma control and attitudes toward treatment in an accessible, real-life adult Asian population.
    PATIENTS AND METHODS: An online survey of 2,467 patients with asthma from eight Asian countries/regions, aged 18-50 years, showed greater than or equal to two prescriptions in previous 2 years and access to social media. Patients were asked about their asthma symptoms, exacerbations and treatment type, views and perceptions of asthma control, attitudes toward asthma management, and sources of asthma information.
    RESULTS: Patients had a mean age of 34.2 (±7.4) years and were diagnosed with asthma for 12.5 (±9.7) years. Half had the Global Initiative for Asthma-defined uncontrolled asthma. During the previous year, 38% of patients visited the emergency department, 33% were hospitalized, and 73% had greater than or equal to one course of oral corticosteroids. About 90% of patients felt that their asthma was under control, 82% considered their condition as not serious, and 59% were concerned about their condition. In all, 66% of patients viewed asthma control as managing attacks and 24% saw it as an absence of or minimal symptoms. About 14% of patients who correctly identified their controller inhalers had controlled asthma compared to 6% who could not.
    CONCLUSION: Patients consistently overestimated their level of asthma control contrary to what their symptoms suggest. They perceived control as management of exacerbations, reflective of a crisis-oriented mind-set. Interventions can leverage on patients' trust in health care providers and desire for self-management via a new language to generate a paradigm shift toward symptom control and preventive care.
    KEYWORDS: asthma control; attitudes; perception
  15. Bhidayasiri R, Hattori N, Jeon B, Chen RS, Lee MK, Bajwa JA, et al.
    Expert Rev Neurother, 2015;15(11):1285-97.
    PMID: 26390066 DOI: 10.1586/14737175.2015.1088783
    Most Parkinson's disease patients will receive levodopa therapy, and of these, the majority will develop some levodopa-induced complications. For many patients, the first complication to develop is the decline in the duration of therapeutic benefit of each levodopa dose, a phenomenon commonly termed 'wearing-off'. There is already extensive literature documenting the epidemiology and management of wearing-off in Parkinson's disease patients of western descent. However, data derived from these studies might not always apply to patients of Asian descent due to genetic variations, differences in co-morbidities or non-availability of certain drugs. This review summarizes the current literature regarding the epidemiology of wearing-off in Asian (including Arab) patients and discusses the management issues in the context of drug availability in Asia.
  16. Wong WF, Kohu K, Nagashima T, Funayama R, Matsumoto M, Movahed E, et al.
    Mol Immunol, 2015 Dec;68(2 Pt A):223-33.
    PMID: 26350416 DOI: 10.1016/j.molimm.2015.08.012
    The Runx1 transcription factor cooperates with or antagonizes other transcription factors and plays essential roles in the differentiation and function of T lymphocytes. Previous works showed that Runx1 is expressed in peripheral CD4(+) T cells which level declines after T cell receptor (TCR) activation, and artificial deletion of Runx1 causes autoimmune lung disease in mice. The present study addresses the mechanisms by which Runx1 contributes to the maintenance of peripheral CD4(+) T cell quiescence. Microarray and quantitative RT-PCR analyses were employed to compare the transcriptome of Runx1 -/- CD4(+) T cells to those of unstimulated and TCR-stimulated Runx1 +/- cells. The results identified genes whose expression was modulated similarly by Runx1 deletion and TCR activation. Among them, genes encoding cytokines, chemokines, and Jak/STAT signaling molecules were substantially induced. In Runx1-deleted T cells, simultaneous increases in Il-17A and Rorγc, a known master gene in TH17 differentiation, were observed. In addition, we observed that the loss of Runx1 reduced the transcription of genes encoding quiescence-associated transcription factors, including Foxp1, Foxo1, and Klf2. Interestingly, we identified consensus Runx1 binding sites at the promoter regions of Foxp1, Foxo1, and Klf2 genes, which can be enriched by chromatin immunoprecipitation assay with an anti-Runx1 antibody. Therefore, we suggest that Runx1 may activate, directly or indirectly, the expression of quiescence-associated molecules and thereby contribute to the maintenance of quiescence in CD4(+) T cells.
  17. Pok KY, Squires RC, Tan LK, Takasaki T, Abubakar S, Hasebe F, et al.
    Western Pac Surveill Response J, 2015 Jun 30;6(2):73-81.
    PMID: 26306220 DOI: 10.5365/WPSAR.2015.6.1.017
    Accurate laboratory testing is a critical component of dengue surveillance and control. The objective of this programme was to assess dengue diagnostic proficiency among national-level public health laboratories in the World Health Organization (WHO) Western Pacific Region.
  18. Yeap SK, Abu N, Mohamad NE, Beh BK, Ho WY, Ebrahimi S, et al.
    PMID: 26335427 DOI: 10.1186/s12906-015-0832-z
    The progression of breast cancer is increasing at an alarming rate, particularly in western countries. Meanwhile, the lower incidence in Asian countries could be attributed to the heavy incorporation of green leaves vegetables or spices in their diets. Murraya koenigii (MK) or often times known as curry leaves are common spice used mostly in tropical countries. Anti-inflammatory and chemopreventive effects of MK aqueous extract on 4T1 breast cancer cell-challenged mice were evaluated.
  19. Lim KS, Tan AH, Lim CS, Chua KH, Lee PC, Ramli N, et al.
    PLoS One, 2015;10(8):e0135470.
    PMID: 26270344 DOI: 10.1371/journal.pone.0135470
    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary stroke caused by mutations in NOTCH3 gene. We report the first case of CADASIL in an indigenous Rungus (Kadazan-Dusun) family in Kudat, Sabah, Malaysia confirmed by a R54C (c.160C>T, p.Arg54Cys) mutation in the NOTCH3. This mutation was previously reported in a Caucasian and two Korean cases of CADASIL. We recruited two generations of the affected Rungus family (n = 9) and found a missense mutation (c.160C>T) in exon 2 of NOTCH3 in three siblings. Two of the three siblings had severe white matter abnormalities in their brain MRI (Scheltens score 33 and 50 respectively), one of whom had a young stroke at the age of 38. The remaining sibling, however, did not show any clinical features of CADASIL and had only minimal changes in her brain MRI (Scheltens score 17). This further emphasized the phenotype variability among family members with the same mutation in CADASIL. This is the first reported family with CADASIL in Rungus subtribe of Kadazan-Dusun ethnicity with a known mutation at exon 2 of NOTCH3. The penetrance of this mutation was not complete during the course of this study.
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