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  1. Fulltext Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene
    Sosnay PR, Siklosi KR, Van Goor F, Kaniecki K, Yu H, Sharma N, et al.
    Nat Genet, 2013 Oct;45(10):1160-7.
    PMID: 23974870 DOI: 10.1038/ng.2745
    Allelic heterogeneity in disease-causing genes presents a substantial challenge to the translation of genomic variation into clinical practice. Few of the almost 2,000 variants in the cystic fibrosis transmembrane conductance regulator gene CFTR have empirical evidence that they cause cystic fibrosis. To address this gap, we collected both genotype and phenotype data for 39,696 individuals with cystic fibrosis in registries and clinics in North America and Europe. In these individuals, 159 CFTR variants had an allele frequency of ł0.01%. These variants were evaluated for both clinical severity and functional consequence, with 127 (80%) meeting both clinical and functional criteria consistent with disease. Assessment of disease penetrance in 2,188 fathers of individuals with cystic fibrosis enabled assignment of 12 of the remaining 32 variants as neutral, whereas the other 20 variants remained of indeterminate effect. This study illustrates that sourcing data directly from well-phenotyped subjects can address the gap in our ability to interpret clinically relevant genomic variation.
    Matched MeSH terms: Cystic Fibrosis/genetics*; Cystic Fibrosis Transmembrane Conductance Regulator/genetics*
  2. Fulltext Detection of F508del mutation in cystic fibrosis transmembrane conductance regulator gene mutation among Malays
    Zilfalil BA, Sarina S, Liza-Sharmini AT, Oldfield NJ, Stenhouse SA
    Singapore Med J, 2006 Feb;47(2):129-33.
    PMID: 16435054
    Cystic fibrosis (CF) is one of the common genetic disorders in the western world. It has been reported to be very rare in Asian populations. According to the Cystic Fibrosis Genetic Analysis Consortium, more than 1,000 mutations of the CF gene have been identified. The CF gene, named the cystic fibrosis transmembrane conductance regulator (CFTR), is located on chromosome 7 and composed of 27 exons. This study aims to detect possible CFTR gene mutations in Malays.
    Matched MeSH terms: Cystic Fibrosis/genetics*; Cystic Fibrosis Transmembrane Conductance Regulator/genetics*
  3. Fulltext CFTR founder mutation causes protein trafficking defects in Chinese patients with cystic fibrosis
    Leung GK, Ying D, Mak CC, Chen XY, Xu W, Yeung KS, et al.
    Mol Genet Genomic Med, 2017 Jan;5(1):40-49.
    PMID: 28116329 DOI: 10.1002/mgg3.258
    Cystic fibrosis (CF) is a rare condition in Asians. Since 1985, only about 30 Chinese patients have been reported with molecular confirmation.
    Matched MeSH terms: Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator
  4. First study of the F508del mutation in Malaysian children diagnosed with cystic fibrosis
    Nathan AM, Thong MK, deBruyne J, Ariffin H
    J Paediatr Child Health, 2011 Aug;47(8):573-5.
    PMID: 21843195 DOI: 10.1111/j.1440-1754.2011.02149.x
    Matched MeSH terms: Cystic Fibrosis/diagnosis; Cystic Fibrosis/genetics*; Cystic Fibrosis Transmembrane Conductance Regulator/genetics*
  5. Fulltext Spectrum of PRSS1, SPINK1, CTRC, CFTR, and CPA1 Gene Variants in Chronic Pancreatitis Patients in Russia
    Litvinova MM, Khafizov KF, Speranskaya AS, Matsvay AD, Asanov AY, Nikolskaya KA, et al.
    Sovrem Tekhnologii Med, 2023;15(2):60-70.
    PMID: 37389024 DOI: 10.17691/stm2023.15.2.06
    The aim of the study was to define the spectrum of genetic risk factors of chronic pancreatitis (CP) development in patients living in the European part of the Russian Federation.

    MATERIALS AND METHODS: The study group included 105 patients with CP, with the age of the disease onset under 40 years old (the average age of onset was 26.9 years). The control group consisted of 76 persons without clinical signs of pancreatitis. The diagnosis of chronic pancreatitis in patients was made on the basis of clinical manifestations and the results of laboratory and instrumental investigations. Genetic examination of patients was conducted using the next-generation sequencing (NGS) technology and included targeted sequencing of all exons and exon-intron boundaries of the PRSS1, SPINK1, CTRC, CFTR, and CPA1 genes. The genotyping of the rs61734659 locus of the PRSS2 gene was also conducted.

    RESULTS: Genetic risk factors of the CP development were found in 61% of patients. Pathogenic and likely-pathogenic variants associated with the risk of CP development were identified in the following genes: CTRC (37.1% of patients), CFTR (18.1%), SPINK1 (8.6%), PRSS1 (8.6%), and CPA1 (6.7%). The frequent gene variants in Russian patients with CP were as follows: CTRC gene - c.180C>T (rs497078), c.760C>T (rs121909293), c.738_761del24 (rs746224507); cumulative odds ratio (OR) for all risk alleles was 1.848 (95% CI: 1.054-3.243); CFTR gene - c.3485G>T (rs1800120), c.1521_1523delCTT (p.Phe508del, rs113993960), and c.650A>G (rs121909046); OR=2.432 (95% CI: 1.066-5.553). In the SPINK1, PRSS1, and CPA1 genes, pathogenic variants were found only in the group of patients with CP. The frequent variants of the SPINK1 gene include c.101A>G (p.Asn34Ser, rs17107315) and c.194+2T>C (rs148954387); of the PRSS1 gene - c.86A>T (p.Asn29Ile, rs111033566); of the CPA1 gene - c.586-30C>T (rs782335525) and c.696+23_696+24delGG. The OR for the CP development for the c.180TT genotype (rs497078) CTRC according to the recessive model (TT vs. CT+CC) was 7.05 (95% CI: 0.86-263, p=0.011). In the CTRC gene, the variant c.493+49G>C (rs6679763) appeared to be benign, the c.493+51C>A (rs10803384) variant was frequently detected among both the diseased and healthy persons and did not demonstrate a protective effect. The protective factor c.571G>A (p.Gly191Arg, rs61734659) of the PRSS2 gene was detected only in the group of healthy individuals and confirmed its protective role. 12.4% of the patients with CP had risk factors in 2 or 3 genes.

    CONCLUSION: Sequencing of the coding regions of the PRSS1, SPINK1, CTRC, CFTR, and CPA1 genes allowed to identify genetic risk factors of the CP development in 61% of cases. Determining the genetic cause of CP helps to predict the disease course, perform preventive measures in the proband's relatives, and facilitate a personalized treatment of the patient in future.

    Matched MeSH terms: Cystic Fibrosis Transmembrane Conductance Regulator/genetics
  6. Fulltext Genome Sequences of Two Pandoraea pnomenusa Isolates Recovered 11 Months Apart from a Cystic Fibrosis Patient
    Ee R, Ambrose M, Lazenby J, Williams P, Chan KG, Roddam L
    Genome Announc, 2015;3(1).
    PMID: 25657265 DOI: 10.1128/genomeA.01389-14
    Pandoraea is an emerging respiratory pathogen capable of causing chronic lung infections in people with cystic fibrosis (CF), but the clinical significance of this infection is ambiguous. We have sequenced and annotated the genomes of two multidrug-resistant Pandoraea pnomenusa isolates recovered 11 months apart from the same CF patient.
    Matched MeSH terms: Cystic Fibrosis
  7. Fulltext Cystic fibrosis in Malay children--a report of three cases
    Norzila MZ, Azizi BH
    Singapore Med J, 1996 Jun;37(3):273-4.
    PMID: 8942227
    Cystic fibrosis (CF) is a rare disease among Asians. Three Malay children with CF presenting with recurrent pulmonary symptoms, malabsorption and failure to thrive are reported. Problems in their management include availability of pancreatic enzymes, compliance to medications and climate factors.
    Matched MeSH terms: Cystic Fibrosis/diagnosis; Cystic Fibrosis/epidemiology*; Cystic Fibrosis/therapy
  8. Fulltext Interventions for preventing and managing advanced liver disease in cystic fibrosis
    Palaniappan SK, Than NN, Thein AW, van Mourik I
    Cochrane Database Syst Rev, 2020 03 30;3:CD012056.
    PMID: 32227478 DOI: 10.1002/14651858.CD012056.pub3
    BACKGROUND: Cystic fibrosis is an autosomal recessive inherited defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene resulting in abnormal regulation of salt and water movement across the membranes. In the liver this leads to focal biliary fibrosis resulting in progressive portal hypertension and end-stage liver disease in some individuals. This can be asymptomatic, but may lead to splenomegaly and hypersplenism, development of varices and variceal bleeding, and ascites; it has negative impact on overall nutritional status and respiratory function in this population. Prognosis is poor once significant portal hypertension is established. The role and outcome of various interventions for managing advanced liver disease (non-malignant end stage disease) in people with cystic fibrosis is currently unidentified. This is an updated version of a previously published review.

    OBJECTIVES: To review and assess the efficacy of currently available treatment options for preventing and managing advanced liver disease in children and adults with cystic fibrosis.

    SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 19 November 2019. We also searched the reference lists of relevant articles and reviews and online trials registries. Date of last search: 01 January 2020.

    SELECTION CRITERIA: Any published and unpublished randomised controlled trials and quasi-randomised controlled trials of advanced liver disease in cystic fibrosis with cirrhosis or liver failure, portal hypertension or variceal bleeding (or both).

    DATA COLLECTION AND ANALYSIS: Authors independently examined titles and abstracts to identify potentially relevant trials, but none were eligible for inclusion in this review.

    MAIN RESULTS: A comprehensive search of the literature did not identify any published eligible randomised controlled trials.

    AUTHORS' CONCLUSIONS: In order to develop the best source of evidence, there is a need to undertake randomised controlled trials of interventions for preventing and managing advanced liver disease in adults and children with cystic fibrosis.

    Matched MeSH terms: Cystic Fibrosis/complications*; Cystic Fibrosis/genetics; Cystic Fibrosis Transmembrane Conductance Regulator/genetics
  9. A systematic review of studies examining the rate of lung function decline in patients with cystic fibrosis
    Harun SN, Wainwright C, Klein K, Hennig S
    Paediatr Respir Rev, 2016 Sep;20:55-66.
    PMID: 27259460 DOI: 10.1016/j.prrv.2016.03.002
    A systematic review was performed (i) to describe the reported overall rate of progression of CF lung disease quantified as FEV1%predicted decline with age, (ii) to summarise identified influencing risk factors and (iii) to review methods used to analyse CF lung disease progression data. A search of publications providing FEV1%predicted values over age was conducted in PUBMED and EMBASE. Baseline and rate of FEV1%predicted decline were summarised overall and by identified risk factors. Thirty-nine studies were included and reported variable linear rates of lung function decline in patients with CF. The overall weighted mean FEV1%predicted over age was graphically summarised and showed a nonlinear, time-variant decline of lung function. Compared to their peers, Pseudomonas aeruginosa infection and pancreatic insufficiency were most commonly associated with lower baseline and more rapid FEV1%predicted declines respectively. Considering nonlinear models and drop-out in lung disease progression, analysis is lacking and more studies are warranted.
    Matched MeSH terms: Cystic Fibrosis/physiopathology*
  10. The role of biochemical testing in cystic fibrosis
    Abdul Rahim FH, Thambiah CS, Samsudin IN, Mohamed Mokhtar N
    Malays J Pathol, 2020 Aug;42(2):297-300.
    PMID: 32860386
    INTRODUCTION: Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder as a result of CF transmembrane conductance regulator gene mutation. It has a wide range of disease severity in patients with the same genotype.

    CASE REPORT: A 5-year-old Malay boy with a history of recurrent pneumonia, presented with productive cough, fever and worsening tachypnoea. Physical examination revealed coarse crepitations, reduced breath sounds and clubbing. Biochemical investigations showed that he had respiratory type 2 failure as a result of bronchiectasis. Sweat conductivity done twice was raised supporting a diagnosis of CF. Other investigations such as bronchoscopy to look for congenital anomaly of the lung, infectious disease screening and tuberculosis, fungal and viral culture and sensitivity were negative. Further cascade screening revealed high sweat conductivity results in his siblings.

    DISCUSSION: Although CF prevalence is low in Malaysia, it is nevertheless an important diagnosis to be recognised as it is associated with increased morbidity.

    Matched MeSH terms: Cystic Fibrosis Transmembrane Conductance Regulator/genetics*
  11. Fulltext The molecular genetics and pathogenesis of cystic fibrosis lung disease
    Abdullah, S.
    Buletin Persatuan Genetik Malaysia, 2006;12(1):10-17.
    MyJurnal
    Cystic Fibrosis (CF) is a life-threatening inherited disease that particularly affects the airways and digestive systems, which is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. CF is considered as the most common autosomal recessive disorder in the Caucasian population. However, the prevalence of this disease amongst Asians is considered to be low, hence the lack of awareness of this disease amongst geneticists and physicians in Malaysia. This review will describe the features of CF, its molecular genetics, the current classification of CFTR mutation classes, the genotype-phenotype correlations, the effects of modifier genes, and the discourse of the disease pathogenesis, in the hope of raising public awareness of the condition and ultimately to improve the clinical and social care of those affected by CF in Malaysia.
    Matched MeSH terms: Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator
  12. Unrecognised infection in a cystic fibrosis patient
    Asiah K, Hanifah YA, Norzila MZ, Hasniah L, Rusanida A
    J Paediatr Child Health, 2006 Apr;42(4):217-8.
    PMID: 16630326
    We report a 17-year-old Malay boy with cystic fibrosis who over a 14-month period experienced worsening respiratory symptoms and deteriorating lung function. Burkholderia pseudomallei was eventually isolated from his sputum. He improved clinically following treatment for meliodosis and his lung function returned to normal.
    Matched MeSH terms: Cystic Fibrosis/drug therapy; Cystic Fibrosis/microbiology*; Cystic Fibrosis/pathology
  13. Testosterone decreases fluid and chloride secretions in the uterus of adult female rats via down-regulating cystic fibrosis transmembrane regulator (CFTR) expression and functional activity
    Mohd Mokhtar H, Giribabu N, Kassim N, Muniandy S, Salleh N
    J Steroid Biochem Mol Biol, 2014 Oct;144 Pt B:361-72.
    PMID: 25125390 DOI: 10.1016/j.jsbmb.2014.08.007
    Estrogen is known to stimulate uterine fluid and Cl(-) secretion via CFTR. This study investigated testosterone effect on these changes in a rat model.
    Matched MeSH terms: Cystic Fibrosis Transmembrane Conductance Regulator/genetics; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism*
  14. Fulltext Supplementation with red palm oil increases β-carotene and vitamin A blood levels in patients with cystic fibrosis
    Sommerburg O, De Spirt S, Mattern A, Joachim C, Langhans CD, Nesaretnam K, et al.
    Mediators Inflamm, 2015;2015:817127.
    PMID: 25688177 DOI: 10.1155/2015/817127
    Patients with cystic fibrosis (CF) show decreased plasma concentrations of antioxidants due to malabsorption of lipid soluble vitamins and consumption by chronic pulmonary inflammation. β-Carotene is a major source of retinol and therefore is of particular significance in CF. The aim of this study was to investigate the effect of daily intake of red palm oil (RPO) containing high amounts of β-carotene on the antioxidant levels in CF patients. Sixteen subjects were recruited and instructed to enrich their food with 2 to 3 tablespoons of RPO (~1.5 mg of β-carotene) daily over 8 weeks. Carotenoids, retinol, and α-tocopherol were measured in plasma at baseline and after intervention. In addition β-carotene, lycopene, α-tocopherol, and vitamin C were measured in buccal mucosa cells (BMC) to determine the influence of RPO on antioxidant tissue levels. Eleven subjects completed the study properly. Plasma β-carotene, retinol, and α-carotene of these patients increased, but plasma concentrations of other carotenoids and α-tocopherol as well as concentrations of β-carotene, lycopene, α-tocopherol, and vitamin C in BMC remained unchanged. Since RPO on a daily basis did not show negative side effects the data suggest that RPO may be used to elevate plasma β-carotene in CF.
    Matched MeSH terms: Cystic Fibrosis/blood*; Cystic Fibrosis/drug therapy*
  15. Fulltext Genistein-induced fluid accumulation in ovariectomised rats' uteri is associated with increased cystic fibrosis transmembrane regulator expression
    Chinigarzadeh A, Kassim NM, Muniandy S, Salleh N
    Clinics (Sao Paulo), 2014 Feb;69(2):111-9.
    PMID: 24519202 DOI: 10.6061/clinics/2014(02)07
    High genistein doses have been reported to induce fluid accumulation in the uteri of ovariectomised rats, although the mechanism underlying this effect remains unknown. Because genistein binds to the oestrogen receptor and the cystic fibrosis transmembrane regulator mediates uterine fluid secretion, we hypothesised that this genistein effect involves both the oestrogen receptor and cystic fibrosis transmembrane regulator.
    Matched MeSH terms: Cystic Fibrosis Transmembrane Conductance Regulator/analysis*; Cystic Fibrosis Transmembrane Conductance Regulator/drug effects*
  16. Chronic suppurative lung disease in a developing country: impact on child and parent
    Nathan AM, Muthusamy A, Thavagnanam S, Hashim A, de Bruyne J
    Pediatr Pulmonol, 2014 May;49(5):435-40.
    PMID: 24482322 DOI: 10.1002/ppul.23001
    To investigate the impact of chronic suppurative lung disease (CSLD) on growth and lung function in the child as well as quality of life of the child and parent.
    Matched MeSH terms: Cystic Fibrosis/complications; Cystic Fibrosis/physiopathology*; Cystic Fibrosis/psychology
  17. Fulltext Candidate Essential Genes in Burkholderia cenocepacia J2315 Identified by Genome-Wide TraDIS
    Wong YC, Abd El Ghany M, Naeem R, Lee KW, Tan YC, Pain A, et al.
    Front Microbiol, 2016;7:1288.
    PMID: 27597847 DOI: 10.3389/fmicb.2016.01288
    Burkholderia cenocepacia infection often leads to fatal cepacia syndrome in cystic fibrosis patients. However, antibiotic therapy rarely results in complete eradication of the pathogen due to its intrinsic resistance to many clinically available antibiotics. Recent attention has turned to the identification of essential genes as the proteins encoded by these genes may serve as potential targets for development of novel antimicrobials. In this study, we utilized TraDIS (Transposon Directed Insertion-site Sequencing) as a genome-wide screening tool to facilitate the identification of B. cenocepacia genes essential for its growth and viability. A transposon mutant pool consisting of approximately 500,000 mutants was successfully constructed, with more than 400,000 unique transposon insertion sites identified by computational analysis of TraDIS datasets. The saturated library allowed for the identification of 383 genes that were predicted to be essential in B. cenocepacia. We extended the application of TraDIS to identify conditionally essential genes required for in vitro growth and revealed an additional repertoire of 439 genes to be crucial for B. cenocepacia growth under nutrient-depleted conditions. The library of B. cenocepacia mutants can subsequently be subjected to various biologically related conditions to facilitate the discovery of genes involved in niche adaptation as well as pathogenicity and virulence.
    Matched MeSH terms: Cystic Fibrosis
  18. Intracellular survival and innate immune evasion of Burkholderia cepacia: Improved understanding of quorum sensing-controlled virulence factors, biofilm, and inhibitors
    Ganesh PS, Vishnupriya S, Vadivelu J, Mariappan V, Vellasamy KM, Shankar EM
    Microbiol. Immunol., 2020 Feb;64(2):87-98.
    PMID: 31769530 DOI: 10.1111/1348-0421.12762
    Burkholderia cepacia complex (Bcc) are opportunistic pathogens implicated with nosocomial infections, and high rates of morbidity and mortality, especially in individuals with cystic fibrosis (CF). B. cepacia are naturally resistant to different classes of antibiotics, and can subvert the host innate immune responses by producing quorum sensing (QS) controlled virulence factors and biofilms. It still remains a conundrum as to how exactly the bacterium survives the intracellular environment within the host cells of CF patients and immunocompromised individuals although the bacterium can invade human lung epithelial cells, neutrophils, and murine macrophages. The mechanisms associated with intracellular survival in the airway epithelial cells and the role of QS and virulence factors in B. cepacia infections in cystic fibrosis remain largely unclear. The current review focuses on understanding the role of QS-controlled virulence factors and biofilms, and provides additional impetus to understanding the potentials of QS-inhibitory strategies against B. cepacia.
    Matched MeSH terms: Cystic Fibrosis/complications; Cystic Fibrosis/immunology; Cystic Fibrosis/microbiology*
  19. Fulltext Bilateral spontaneous persistent open pneumothorax with chylothorax
    Khajotia R, Raman S
    Can Fam Physician, 2012 Jul;58(7):757-60.
    PMID: 22859639
    Matched MeSH terms: Cystic Fibrosis/diagnosis
  20. Testosterone regulates levels of cystic fibrosis transmembrane regulator, adenylate cyclase, and cAMP in the seminal vesicles of orchidectomized rats
    Ramli NS, Giribabu N, Muniandy S, Salleh N
    Theriogenology, 2016 Jan 15;85(2):238-46.
    PMID: 26483308 DOI: 10.1016/j.theriogenology.2015.09.036
    Secretions of chloride (Cl(-))- and bicarbonate (HCO3(-))-rich fluid by the seminal vesicles could involve cystic fibrosis transmembrane regulator (CFTR), which activity can be stimulated by cAMP generated from the reaction involving adenylate cyclase (AC). In this study, we investigated levels of CFTR, AC, and cAMP in the seminal vesicles under testosterone influence. Orchidectomized adult male rats received 7-day treatment with 125 or 250 μg/kg/day of testosterone with or without flutamide or finasteride. At the end of the treatment, animals were sacrificed and seminal vesicles were harvested for analyses of CFTR and AC protein expression level by Western blotting. Distribution of CFTR and AC in seminal vesicles was observed by immunohistochemistry. Levels of cAMP and dihydrotestosterone in seminal vesicle homogenates were measured by ELISA. Cystic fibrosis transmembrane regulator, AC, and cAMP levels increased with increasing doses of testosterone (P Cystic fibrosis transmembrane regulator and AC were expressed at the apical membrane of the epithelium lining the seminal vesicle lumen with higher expression levels observed in testosterone-treated rats than in non-treated orchidectomized rats (P 
    Matched MeSH terms: Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator
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