Delta F508 Research Articles

Recurrent Wheezing in a Child: Unraveling Atypical Presentations of Cystic Fibrosis and Polymorphisms: A Case Report

Background: Cystic Fibrosis (CF), is the most common, life-limiting, single-gene disease affecting the Caucasian population, with a reported incidence of1/3500 births. It is inherited in an autosomal recessive fashion and its diagnosis is notably challenging, since in several cases CF may not be detected by the newborn screening test and the sweat test, which are frequently reported negative of with doubtful results, especially in cases with atypical symptoms at onset or with uncommon mutations or polymorphisms. Case Presentation: In this case, we present a case of CF presented with recurrent wheezing, reporting multiple negative or borderline sweat tests. The genetic evaluation revealed delta F508 (CF- causing) and heterozygous poly T5 polymorphism TG11 (TG)11T5. Conclusion: The importance of this case lies in the recognition of wheezing as a symptom and not as a disease, thus many conditions such as CF have to be considered in its diagnostic process. Finally, it is of utmost importance to bear in mind that many mutations or polymorphisms might evade newborn screening and sweat tests.

THU294 Glucagon Like Peptide-1 Analogue Therapy In Obese Patients With Cystic Fibrosis Related Diabetes

Abstract Disclosure: A.R. Ankireddypalli: None. A. Moheet: None. Introduction: Cystic fibrosis (CF) has classically been associated with malnutrition and being underweight. Intense emphasis on nutritional augmentation and advancement in medical therapies including recent introduction of CFTR modulators have significantly reduced the prevalence of malnutrition in CF. However, this success has been accompanied by a significant rise in overweight/obesity in CF. Recent studies have reported that one-third of all adult CF patients are overweight or obese. Glucagon like peptide receptor-1 agonists (GLP-1RA) therapy is an effective treatment for type 2 diabetes mellitus (T2DM) and obesity. Current guidelines for CF related diabetes (CFRD), recommend insulin as the mainstay of treatment. However, with increase in prevalence of obesity, there is increased interest in examining the role of incretin-based therapies in CFRD. Gastrointestinal (GI) symptoms like abdominal pain, steatorrhea, gastroparesis are common in CF. Concerns about the potential GI side effects had previously dampened the enthusiasm for these drugs in CF.The objective of this case series is to demonstrate impact on glycemic control and weight, and tolerability of GLP1-RA treatment in obese patients with CFRD and pancreatic insufficiency (PI) after 1 year of therapy. Case 1: A 21-year-old female with CF (delta F508 homozygote) and PI, was diagnosed with CRFD at 15 years. She was initially on lantus 14 units daily with HbA1c of 6.7%. She was started on CFTR modulator therapy and with increase in BMI from 37 to 45 in 1 year with HbA1c of 8.9%. She was started on semaglutide and tolerated the medication well with no GI side effects. 1 year later her BMI reduced to 42 and HbA1c was 8.2%. Case 2: A 62-year-old male with CF (delta F508 heterozygote) and PI, diagnosed with CFRD at age 44 years. He was on lantus 66 units and aspart 1 unit per 5 grams carbohydrate coverage. He was started on CFTR modulator and in 1 year BMI increased from 53 to 57. He was started on semalglutide, which he tolerated well with no GI symptoms. 1 year later his Hba1c improved to 7% with a BMI of 54. Discussion: In this era of CFTR modulator therapy, CF patients are faced with changing metabolic parameters, including weight gain and developing T2DM phenotype with insulin resistance. There is one previous case report of short duration of GLP-1RA use in CFRD. We report > 1 year of clinical experience of GLP-1RA use in 2 patients. GLP-1RA was well tolerated in these patients with improvement in glycemic control and weight loss. GLP-1 RA should be considered in obese, PI patients with CFRD as an add-on therapy to insulin. However, larger studies with long-term follow up are required to study the full impact of GLP-1RA to establish it as a treatment option in CFRD. Presentation: Thursday, June 15, 2023

Prevalence of tracheobronchomalacia is higher than previously reported in children with cystic fibrosis.

Tracheobronchomalacia (TBM) is estimated to be present in 1 in 2100 children. Previous reports suggest the prevalence is higher in children with cystic fibrosis (CF). This has clinical implications with potential to influence airway clearance and lung health. To determine the prevalence and clinical associations of TBM in Western Australian children with CF. Children with CF born between 2001 and 2016 were included. Operation reports from bronchoscopies performed until the age of 4 were retrospectively reviewed. Data were collected on the presence, persistence defined as a repeat diagnosis, and severity of TBM. Data on genotype, pancreatic status, and symptoms at CF diagnosis were extracted from the medical record. Associations between categorical variables were compared using χ2 and Fisher's exact test. Of 167 children (79 male), 68 (41%) were diagnosed with TBM at least once, with TBM persistent in 37 (22%) and severe in 31 (19%). TBM was significantly associated with pancreatic insufficiency (χ2 = 7.874, p < 0.05, odds ratio [OR] 3.4), delta F508 gene mutation (χ2 = 6.489, p < 0.05, OR 2.3), and a presentation of meconium ileus (χ2 = 8.615, p < 0.05, OR 5.0). Severe malacia was less likley in females (χ2 = 4.523, p < 0.05, OR 0.42) . No significant relationship was found with respiratory symptoms at the time of CF diagnosis (χ2 = 0.742, p = 0.39). TBM was common in this group of children under the age of 4 with CF. A high index of suspicion for airway malacia should be considered in children with CF, particularly those who present with meconium ileus and have gastrointestinal symptoms at diagnosis.

Clinical outcomes of digital health in adults with cystic fibrosis

BackgroundThe aim of this study was to assess the long-term clinical impact of the application of e-health as part of a virtual model of care in patients with Cystic Fibrosis (CF). MethodsDigital care group (DCG) were deemed suitable for using the NuvoAir Home platform to monitor their disease at home as part of a virtual model of care project. The usual care group (UCG) remained on usual care. NuvoAir Home platform consists of a smartphone application, Bluetooth spirometer and a clinician portal. Data on pulmonary function, Cystic Fibrosis Questionnaire–Revised (CFQR) and pulmonary exacerbations were collected at baseline and after twelve months. A survey for the digital care group was emailed to evaluate their experience using the technology. ResultsBetween February 2020 and May 2020 a cohort of 43 CF patients were recruited for the DCG (26 females; mean age 31.6 ± 6.8; 16 homozygous for delta F508; FEV1 48.4 ± 16.3% predicted) and 36 CF patients for UCG (18 females; mean age 29.1 ± 9.4; 6 homozygous for delta F508; FEV1 77.0 ± 25.0% predicted). CFQ-R score improved significantly through 12 months in the DCG with a mean change of 13.8 points, p < 0.0001, and no changes for the UCG (p = 0.73). When we analyzed the subgroup of CF patients on digital and usual care who did not receive CFTR modulator therapy, we found a change in CFQ-R score which was significantly associated with the use of digital technology while adjusting for baseline differences (p = 0.020). There was no significant difference in the change in lung function and number of exacerbations. 90% of patients reported they understood their CF better using the NuvoAir Home platform. No changes in medical treatment were reported during that time. ConclusionsThe application of digital technologies in the management of adults with CF showed an improvement in patients’ quality of life. Using a virtual model of care was well accepted by CF patients and improved their understanding of their medical condition.

Distal intestinal obstruction syndrome: a diagnostic and therapeutic challenge in cystic fibrosis

ObjectiveTo evaluate the demographics, genotype, and clinical presentation of pediatric patients presenting with distal intestinal obstruction syndrome (DIOS), and factors associated with DIOS recurrence. MethodsCase series of ten patients (median age 13.2 years), followed‐up in a reference center, retrospectively assessed. Data analyzed included age, gender, cystic fibrosis genotype, meconium ileus at birth, hydration status, pulmonary exacerbation, Pseudomonas aeruginosa colonization, pancreatic insufficiency (PI), body mass index (BMI) at the episodes, clinical manifestations of DIOS, imaging studies performed, acute management of DIOS, maintenance therapy, and recurrence on follow‐up. ResultsAll patients had two positive sweat chloride tests, and nine of ten also had genotype study. The most common genotype identified was homozygosis for the delta F508 mutation. In seven cases, a previous history of meconium ileus was reported. All patients had pancreatic insufficiency. Diagnosis of DIOS was based on clinical and imaging findings. Of the total number of episodes, 85% were successfully managed with oral osmotic laxatives and/or rectal therapy (glycerin enema or saline irrigation). Recurrence was observed in five of ten patients. ConclusionIn this first report of pediatric DIOS in South America, the presence of two risk factors for DIOS occurrence was universal: pancreatic insufficiency and severe genotype. Medical history of meconium ileus at birth was present in most patients, as well as in the subgroup with DIOS recurrence. The diagnosis relied mainly on the clinical presentation and on abdominal imaging. The practices in the management of episodes varied, likely reflecting changes in the management of this syndrome throughout time.

Distal intestinal obstruction syndrome: a diagnostic and therapeutic challenge in cystic fibrosis

ObjectiveTo evaluate the demographics, genotype, and clinical presentation of pediatric patients presenting with distal intestinal obstruction syndrome (DIOS), and factors associated with DIOS recurrence. MethodsCase series of ten patients (median age 13.2 years), followed-up in a reference center, retrospectively assessed. Data analyzed included age, gender, cystic fibrosis genotype, meconium ileus at birth, hydration status, pulmonary exacerbation, Pseudomonas aeruginosa colonization, pancreatic insufficiency (PI), body mass index (BMI) at the episodes, clinical manifestations of DIOS, imaging studies performed, acute management of DIOS, maintenance therapy, and recurrence on follow-up. ResultsAll patients had two positive sweat chloride tests, and nine of ten also had genotype study. The most common genotype identified was homozygosis for the delta F508 mutation. In seven cases, a previous history of meconium ileus was reported. All patients had pancreatic insufficiency. Diagnosis of DIOS was based on clinical and imaging findings. Of the total number of episodes, 85% were successfully managed with oral osmotic laxatives and/or rectal therapy (glycerin enema or saline irrigation). Recurrence was observed in five of ten patients. ConclusionIn this first report of pediatric DIOS in South America, the presence of two risk factors for DIOS occurrence was universal: pancreatic insufficiency and severe genotype. Medical history of meconium ileus at birth was present in most patients, as well as in the subgroup with DIOS recurrence. The diagnosis relied mainly on the clinical presentation and on abdominal imaging. The practices in the management of episodes varied, likely reflecting changes in the management of this syndrome throughout time.

Cystic fibrosis presentation in del. F508 and p. Tyr109Glyfs compound heterozygote CFTR state: a case report

The diagnosis of cystic fibrosis (CF) is commonly confirmed by molecular genetics with the presence of specific mutations of cystic fibrosis transmembrane conductance regulator (CFTR) gene. We report a case of cystic fibrosis (CF) in a 15-year-old female patient who is a compound heterozygote for CFTR gene, with delta F508 and Tyr109Glyfs mutations detected. This is the first detailed description of such a case in the medical literature. The primary CF presentation occurred at the age of 9 in the form of gastrointestinal symptoms including greasy, bulky, and foul-smelling stool. The patient exhibited delayed growth, with her height and weight being below the 5th centile for age according to the World Health Organization growth curves. Pancreatic enzyme supplement treatment was started immediately, alongside high-fat and high-calorie diet, resulting in patient’s recovery and development. DNA analysis of CFTR gene demonstrated the presence of del. F508 mutation and a rare combining deletion and insertion mutation p. Tyr109Glyfs. The combination of the two mutations is very rare in CF patients and is therefore valuable to document this case in order to provide information on disease progression, therapy options, and outcomes. With standard treatment and early diagnosis, the patient is currently doing well and is not restricted by the disease in her daily and sports activities.

Phenotypic spectrum and genetic heterogeneity of cystic fibrosis in Sri Lanka

BackgroundCystic fibrosis has been largely under-diagnosed and thus, limited data is available on the incidence of cystic fibrosis in Sri Lanka. Our aim is to describe the phenotypic and genotypic spectrum of children with cystic fibrosis in Sri Lanka.Case presentationThis report describes 10 unrelated cystic fibrosis cases with phenotypic features of cystic fibrosis and abnormal or intermediate sweat tests. The most common phenotypic features in this sample of symptomatic patients were persistent or recurrent lower respiratory tract infections, failure to thrive and Pseudo-Bartter syndrome. Altogether 7 cystic fibrosis causing mutations were identified in 10 patients. Except delta F508 which is the commonest mutation worldwide all the other mutations detected in Sri Lankan patients are rare mutations. 1161delC and V456A detected in our patients are South Asian mutations. The other mutations such as [C.1282C > G; C.2738A > G], C.53 + 1G > C, 2184insA and a deletion encompassing exons 4 to 11 have been reported previously from European patients with cystic fibrosis.ConclusionThese cases highlight the importance of considering the diagnosis of cystic fibrosis in children and young adults presenting with persistent respiratory tract infections associated with severe malnutrition and Pseudo-Bartter syndrome, especially in low income countries where newborn screening for cystic fibrosis is not available. The spectrum of CFTR mutations in Sri Lanka is heterogeneous and possibly linked to genetic flow from Indian subcontinent and Europe. The common mutations should be identified by sequencing the entire CFTR gene in adequate number of cystic fibrosis patients in order to design a mutation panel for common regional mutations.

The Cystic Fibrosis-Like Airway Surface Layer Is not a Significant Barrier for Delivery of Eluforsen to Airway Epithelial Cells.

Background: Eluforsen (previously known as QR-010) is a 33-mer antisense oligonucleotide under development for oral inhalation in cystic fibrosis (CF) patients with the delta F508 mutation. Previous work has shown that eluforsen restores CF transmembrane conductance regulator (CFTR) function in vitro and in vivo. To be effective, eluforsen has first to reach its primary target, the lung epithelial cells. Therefore, it has to diffuse through the CF airway surface layer (ASL), which in CF is characterized by the presence of thick and viscous mucus, impaired mucociliary clearance, and persistent infections. The goal of this study was to assess delivery of eluforsen through CF-like ASL. Methods and Results: First, air-liquid interface studies with cultured primary airway epithelial cells revealed that eluforsen rapidly diffuses through CF-like mucus at clinically relevant doses when nebulized once or repeatedly, over a range of testing doses. Furthermore, eluforsen concentrations remained stable in CF patient sputum for at least 48 hours, and eluforsen remained intact in the presence of various inhaled CF medications for at least 24 hours. When testing biodistribution of eluforsen after orotracheal administration in vivo, no differences in lung, liver, trachea, and kidney eluforsen concentration were observed between mice with a CF-like lung phenotype (ENaC-overexpressing mice) and control wild-type (WT) littermates. Also, eluforsen was visualized in the airway epithelial cell layer of CF-like muco-obstructed mice and WT littermates. Finally, studies of eluforsen uptake and binding to bacteria prevalent in CF lungs, and diffusion through bacterial biofilms showed that eluforsen was stable and not absorbed by, or bound to bacteria. In addition, eluforsen was found to be able to penetrate Pseudomonas aeruginosa biofilms. Conclusions: The thickened and concentrated CF ASL does not constitute a significant barrier for delivery of eluforsen, and feasibility of oral inhalation of eluforsen is supported by these data.

Features of changes in the quality of life in cystic fibrosis patients against the background of its effective treatment

For the determination of characteristics of LQ ofpatients with cystic fibrosis (CF) and evaluation of the efficacy of the management there was used Health Utilities Index (HUI) questionnaire. The study involved 99 CF patients at the age of from 5 to 18 years. The comparison group - 102 conditionally healthy peers of the same age. All children underwent to a comprehensive medical examination and treatment. LQ assessment was carried with the aid of the HUI questionnaire. CF patients were found to have a significant decline in overall LQ in 84,8% of cases in comparison with their healthy peers. Analysis of the «way of life cohort» showed the fall in multiattribute utility indices in children at the age of 6.12 and 16 years. There was also noted a pronounced decline of indices on attributes: «pain» in 55,6%, «emotions» - in 65,6% and the «self-care» - in 20,2% of cases. Factors significantly affecting on LQ of CF patients were established to be: the presence of homozygous or heterozygous delta F508 mutation, disturbances of the respiratory function and malnutrition, which contributed to a decrease as in the overall index as well in specific aspects of LQ. Against the background of the management during the one hospitalization there was noted the positive dynamics due to the gain in the index of the emotional background. A similar situation was revealed after 6 months in re-hospitalization. Pronounced positive dynamics was noted after the management of patients with severe course of the disease, the worst values of radiological indices and a decline in FEV1 indices. The authors believe the study of LQ of CF patients to be important not only for the evaluation of the impact of the disease on the patient’s LQ, but also for the determination of the efficacy of the management.

Novel mutations and deletions in cystic fibrosis in a tertiary cystic fibrosis center in Istanbul.

Cystic fibrosis (CF) genotyping has garnered increased attention since the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989 led to the identification of over 1700 mutations on chromosome 7. Yet, little is known about the genetic profile of CF patients in Turkey. This study sought to determine the mutation distribution among CF patients seeking care at Marmara University. Two hundred fifty previously diagnosed CF patients were included in the study. CFTR gene exons 1 to 27 were amplified by a polymerase chain reaction and whole DNA sequencing was performed. Duplications and deletions were investigated by the multiplex ligation-dependent probe amplification (MLPA) technique in patients with one or two unidentified mutations in sequence analysis. CFTR mutation analysis revealed 80 mutations and five large deletions were present in our study population. The five most common mutations were (delta) F508 (c.1521-1523delCTT) (28.4%), 1677delTA (c.1545-1546delTA) (6.4%), 2789 + 5G- > A (c.2657 + 5G > A) (5.8%), N1303K (c.3909C > G) (2.4%), and c.2183AA- > G (c.2051-2052delAAinsG) (4.0%). Large deletions were found in 16 patients. Four novel mutations and two novel deletions were detected in this study. We have identified four novel mutations and two novel deletions using next-generation DNA sequencing and the MLPA technique and obtained an overall mutation detection rate of 91.4%. Detection of novel variants in CF patients will assist in genetic counseling and in determining appropriate patients for new therapies.

Comparison of Homozygous for Delta F508 Mutation Nutritional Status, Lung Function Outcomes, Bacterial Growth, Antibiotic Treatments and Therapeutic Outcomes between the Amish and Non-Amish in a Single Pediatric Cystic Fibrosis Centre: A Retrospective Case-Controlled Study

There exists evident differences in the health and the care received of the Amish people in comparison to the general population. Amish patients were 100% homozygous for delta F508 mutation versus 12% in the non-Amish population (P=0.057). The Amish community was prescribed dietary supplements at a rate of 89% versus 50% for non-Amish (P=0.087). BMI > 75th percentile was 51.25% in Amish patients and 61.25% in non-Amish patients (P=0.31). Mean FEV1 value was 83.6% versus 100% while mean FEF 25-75 value was 58% versus 86% for Amish and nonAmish people respectively. There was substantial variance in the number of episodes of the same infection per patient between Amish and non-Amish population (1 IQR 0–1 versus 0 IQR 0–1; p=0.012). The rate of antibiotic prescribing per patient in the Amish group was 7.9 perceptions versus 2.2 prescriptions. The study aims to create the best possible treatment and the highest quality of life for patients with cystic fibrosis. Our manuscript creates a paradigm for future studies on the delta F508 mutation, nutrition supplements, body mass index (BMI), forced expiratory volume in 1 second (FEV1), forced expiratory flow (FEF 25-75), airway microbial organisms and changes in antibiotic treatments in Amish compared to the non-Amish group, as well as developing a platform for an Amish community health program.

Pediatric Case Series of Cystic Fibrosis, Diabetes, and Islet Cell Autoimmunity.

Diabetes is the most common comorbidity in individuals with cystic fibrosis (CF). Among people with CF, the prevalence of CF-related diabetes (CFRD) is estimated to be 2% in children, 19% in adolescents, 40% in individuals in their 20s, and 45–50% in those ≥30 years of age (1). CFRD shares some aspects with type 1 diabetes in that it is primarily due to insulin deficiency, but it is distinguished from type 1 diabetes because of its insidious onset over years and the persistence of some insulin production long after diagnosis, which makes diabetic ketoacidosis (DKA) very rare in CFRD (2). Routine screening for type 1 diabetes autoantibodies is not recommended for patients with CF and hyperglycemia (3). However, the following three cases illustrate certain instances that may warrant checking for type 1 diabetes autoantibodies (i.e., hyperglycemia before age 10, symptomatic presentation, and DKA; increasing insulin requirement; or presence of other autoimmune diseases or family history of autoimmune diseases in a CF patient). ### Patient 1 Patient 1 is a non-Hispanic white male with CF (genotype delta F508 homozygous), pancreatic insufficiency, and CF-related liver disease who presented at 16 years of age with polyuria, polydipsia, dry mouth, and weight loss of 5 kg over 3 months. His family history was positive for hypothyroidism in his father and CF in his sister and negative for diabetes. His height was 152 cm (<1st percentile), his weight was 41.6 kg (<1st percentile), and his BMI was 18.0 kg/m2 (12th percentile). Physical examination showed normal mental status, no Kussmaul breathing, dry mucous membranes, and clubbing. Laboratory evaluation revealed fasting glucose of 350 mg/dL, pH 7.42, bicarbonate 24 mEq/L, blood urea nitrogen (BUN) 22 mg/dL, and creatinine 0.6 mg/dL. Urinalysis showed +3 glucose and +1 ketones. His C-peptide level was 1.1 ng/mL (normal range 1.1–4.4 ng/mL), and his …

Bridging for lung transplantation with lumacaftor/ivacaftor

The case of a young female cystic fibrosis patient, homozygous for delta F508 and with terminal respiratory insufficiency, who started treatment with lumacaftor/ivacaftor http://ow.ly/4I0t30kftDx

F508del CFTR gene mutation in patients with allergic bronchopulmonary aspergillosis

ABSTRACTObjective: The F508del mutation occurs in approximately 3.5% of Caucasian population of Northern Europe. Heterozygotes have increased risk for asthma and reduced pulmonary function. Allergic bronchopulmonary aspergillosis (ABPA) is more common in patients with cystic fibrosis (CF). We aimed to establish the frequency of F508del mutation in adult patients with ABPA. Methods: A retrospective matched case-control study of CF genotyped patients with ABPA seen at the National Aspergillosis Centre was undertaken. Key data were collected retrospectively from medical records, including respiratory comorbidities, total IgE, Aspergillus IgG and IgE, and immunoglobulins. Cystic fibrosis transmembrane regulator (CFTR) gene mutation analysis included multiplex PCR and sequencing. Results: From a cohort of 189 ABPA patients, 156 were screened for common mutations and variants in the CFTR gene. Eighteen were heterozygous for at least one CFTR mutation; 12 (7.7%) were heterozygous for the F508del, notably; 3 were heterozygous for the intron 8 5T variant; and 1 for an intronic variant of uncertain significance, c.3139 + 18C>T. Eight (67%) had asthma, 7 (58%) had CT-defined bronchiectasis, 4 (33%) hypergammaglobulinemia (>16 g/L), 3 (25%) sinusitis and 1 (8%) chronic pulmonary aspergillosis. Eight (67%) had elevated Aspergillus IgG antibodies (42–98 mg/L), and 8 (67%) had total IgE above 1,000 KIU/L. Two individuals heterozygous for the F508del mutation and the TG12T5 variant were diagnosed with CF, leading to a de novo CF discovery rate of 1.3%. Conclusions: In our ABPA patient cohort, the presence of the delta F508 mutation was higher than that seen in general population. Genetic counseling for CFTR genotyping might be appropriate for these patients.

Cystic Fibrosis Mutation Detection with SPR Biosensor in Real Samples via Multiple Surfaces Binding Method.

Surface Plasmon Resonance (SPR) based biosensor system was developed for the detection of Delta F508 (ΔF508del) Cystic Fibrosis (CF) mutation in both synthetic and real samples. In order to provide an effective hybridization between probe and the Polymerase Chain Reaction (PCR) amplicons (target), streptavidin was bound to the surface and biotin-tag probe was sent to the streptavidin-coated surface. For the target preparation, blood samples were collected from the patients who suffer from CF. Following the DNA isolation; samples were amplified with PCR with biotin-tag. Before sending the biotin-tag PCR amplicons onto the modified surface, amplicons were also interacted with the helper oligonucleotides to prevent re-annealing of the denatured DNA strands. This kind of 'multiple surface binding' method helps increasing the sensitivity of the detection. The limit of detection (S/N= 3) was calculated as 12.24 pico-mole/ml for PCR-like synthetic long target sequence and 13x105 molecules for real samples in less than half an hour. Using the both biotin-tag probe and the helper oligonucleotides together, hybridization was achieved much more efficiently than traditional denaturation protocols for real samples and biotinfree hybridization detection. To the best of our knowledge, the procedure described in this study is one of the simplest, rapid and sensitive methods for CF mutation detection with SPR based biosensor system in real samples.

Cover Image: Aquagenic wrinkling of the palms: a clue to underlying cystic fibrosis heterozygosity

Conflicts of interest: none declared. Dear Editor, Within 2 min of water immersion, this patient developed characteristic changes of aquagenic wrinkling of the palms (AWP). A rare dermatosis, AWP is distinguished by the transient appearance of white oedematous papules and plaques amid excessive wrinkling of volar skin within minutes of water exposure. It is common in cystic fibrosis (CF),1 and is reported in 9–25% of CF carriers.2 Despite having an unremarkable family history, our patient carried the often associated delta F508 mutation in CFTR. Although not validated, the timing to symptom onset may distinguish carrier status. Given the associations, CF screening and genetic testing should be considered for all patients with AWP.

Clinical and laboratory profile of children with Cystic Fibrosis: Experience of a tertiary care center in Pakistan.

Objective:To determine the clinical presentation, diagnostic investigations and laboratory workup done in admitted children with cystic fibrosis at Aga Khan University Hospital Karachi, Pakistan.Methods:This is athree years retrospective study from January 2013 to December 2015 conducted at The Aga Khan University Hospital Karachi Pakistan, enrolling admitted patient from birth to 15 years of either gender, diagnosed with CF on the basis of clinical features and positive sweat chloride test. Different clinical presentations were noted including initial presentations. Sweat chloride values more than 60mmol/L were labeled as positive and consistent with diagnosis of CF. Available Delta F-508 mutation analyses were noted. Relevant laboratory and radiological investigations including sputum culture and HR-CT chest findings were documented. Results were analyzed using SPSS version 20.Results:Total 43 children were selected according to the inclusion criteria. Chronic cough (69.76%) was the most common initial clinical presentation. Mean age at onset of symptoms was 14.41± 26.18 months and mean age at diagnosis was 47.20 ± 45.80 months Respiratory features were most common in our cohort including chronic productive cough (90.71%), recurrent bronchopneumonia (72.09%) and asthma like presentation (44.19%) with wheezing and cough. 86% patients presented with failure to thrive. Gastroenterological features including steatorrhea were seen in 55.81% patients and 44.19% patients had abdominal distension. Mean sweat chloride value in our population was 82.70± 22.74. Gene analysis for Delta F-508 was identified in 12 (27.90%) patients. Bronchiectatic pulmonary changes on HRCT were seen in 18 patients (41.86%). Pseudomonas grew in 12 patients (27.90%) in sputum cultures at the time of diagnosis.Conclusion:Respiratory presentations predominate in CF children followed by gastrointestinal features. Nearly half of our patient had bronchiectatic changes on CT scan chest and more than quarter had pseudomonas colonization in the airways at the time of diagnosis. Delta F-508 mutation was found to be uncommon in our study population. There is significant delay in diagnosing patients with CF.

Further Evidence That the CFTR Variant c.2620-6T&gt;C Is Benign

The c.2620-6T>C variant in the CFTR gene is a rare variant about which little is known. We present an asymptomatic adult who has this variant as well as the well described delta F508 pathogenic variant in transpresentation. This patient provides additional evidence that this is a benign polymorphism.

Electrochemical Determination of Cystic Fibrosis Gene Mutation by Magnetic Beads-Based Disposable Kit-type Biosensor

This paper introduces a disposable magnetic beads-based DNA biosensor for the rapid, sensitive and selective detection of Delta F508 (ΔF508del) Cystic Fibrosis (CF) gene mutation for the first time. The developed protocol contains the use of streptavidin-coated magnetic beads (MBs) and disposable screen printed carbon electrodes (SPEs). In the study, biotin-tagged specific capture probe was firstly immobilized on streptavidin-coated MBs and the modified beads were stored at 4°C in the form of a “kit” until the analysis of target DNA. The probe contained easy-constructed MBs kit was then incubated with the target DNA for hybridization. The detection of hybridization was identified based on enzymatic (alpha naphthol signal-based) or label-free (guanine signal-based) methods by using differential pulse voltammetry (DPV). The genosensor response was stable up to 6 months of storage period of the kit and the detection limit (LOD) of 0.5 picomole in 45 μL of sample volume was obtained for a 18-mer synthetic target with in 30 min detection time.