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Meconium ileus
Published in Mark Davenport, James D. Geiger, Nigel J. Hall, Steven S. Rothenberg, Operative Pediatric Surgery, 2020
Robert J. Vandewalle, Frederick J. Rescorla
Cystic fibrosis (CF) is the most common serious inherited defect affecting the Caucasian population. CF is transmitted as an autosomal recessive condition with a 5% carrier rate and an incidence of approximately 1 in 2500 live births. The CF transmembrane conductance regulator (CFTR) gene is located on the long arm of chromosome 7. According to the Cystic Fibrosis Genetic Analysis Consortium, 13 mutations occur at a frequency of greater than 1% and account for 87% of CF alleles. The delta F508 mutation is the most common and is present in 70% of CF alleles in the United States. There are great differences among populations, and among African Americans delta F508 accounts for only 43% of the alleles. The CFTR protein controls sodium and chloride transport and in CF this results in abnormal luminal secretions. Neonatal intestinal obstruction due to inspissated meconium has been identified since the early reports concerning CF and is referred to as meconium ileus. This presentation is observed in up to 20% of infants born with CF. The etiology of this abnormal meconium (mucoviscidosis) is due to deficient pancreatic and intestinal secretions, as well as an abnormal concentration of the meconium within the duodenum and proximal jejunum. Instances of meconium ileus can be classified into uncomplicated and complicated cases.
Gene Therapy for Chronic Inflammatory Diseases of the Lungs
Published in Kenneth L. Brigham, Gene Therapy for Diseases of the Lung, 2020
With an incidence of 1 in 2500 live births, CF is the most common lethal genetic disease in Caucasians (28). It rarely affects individuals of African or Asian ancestry. CF is characterized by a defect in epithelial chloride channel activity caused by mutations in the CF transmembrane conductance regulator (CFTR) gene (29-31). This gene, located on chromosome 7, consists of approximately 250,000 bp and encodes for an mRNA of 6.5 kb (32). Over 350 mutations have been identified; however, more than 70% of individuals afflicted with CF carry the delta F508 genetic defect.
Genetics and metabolic disorders
Published in Jagdish M. Gupta, John Beveridge, MCQs in Paediatrics, 2020
Jagdish M. Gupta, John Beveridge
The sister is heterozygous meaning that she has only one copy of the CF mutation (Delta F508). Both her parents carry Delta F508 so neither of them could pass on a different CF mutation or they would be CF affected themselves. She is, therefore, a CF carrier-not CF affected. Siblings of CF individuals, provided they do not have CF, each have a 2 in 3 chance of carrier status. Chinese are far less likely to be CF carriers than are Caucasians, in whom 1 in 25 individuals is a carrier. Therefore the risk to offspring for this couple is very low (1% is the risk if the husband is of North European/Caucasian origin.) CF males are infertile. The majority of CF individuals are homozygous for DeltaF 508. Consanguinity is unlikely in a recessive disorder where the gene frequency is relatively common.
Severe asthma and cystic fibrosis: Overlapping phenotypes?
Published in Canadian Journal of Respiratory, Critical Care, and Sleep Medicine, 2019
Giovanna Riolo, Kelly M. Rodrigues, Cathy E. Dai, Andrew G. Day, M. Diane Lougheed
Most mutations identified in this cohort were uncommon and may have minimal residual CFTR function. For instance, in the case of patient 4 in Table 4, the patient was labeled CFTR-RD because she has one mutation that is disease causing (Delta F508) and one mutation that is associated with CFTR-RD (p.Val470Met).9 Most individuals with p.Val470Met mutation when combined with another CF-causing mutation will be healthy. A small number of individuals may develop mild symptoms or be diagnosed with a CFTR-RD. Our patient did not meet criteria for CF. Patient 9 in Table 4 is a unique case of CFTR-RD. R117C is a CF-causing mutation and G576A mutation is associated with CFTR-RD.23 Whether or not this is associated with disease, particularly in the setting of complex alleles, is debatable.
A novel CFTR gene variant – p.Tyr517* associated with cystic fibrosis: a case report
Published in Fetal and Pediatric Pathology, 2018
Pratiksha Chheda, Tavisha Dama, Dollar Goradia, Shailesh Pande, Sushant Vinarkar
Cystic fibrosis (CF), an autosomal recessive disorder, is caused by mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene. The frequency of CF varies across the globe and 1 in every 2000–3000 in European Union and 1 in 3500 newborns in United States of America is affected by CF [1]. CF in India is estimated to occur at a frequency of 1:10,000 to 1:40,000 as indicated by studies on migrant Indian population in United States and United Kingdom [2]. More than 1000 different mutations are known to cause CF, delta F508 being most common. The classic or typical form of CF affects mainly the respiratory tract, gastrointestinal tract, male reproductive tract, and sweat glands and is caused by loss-of-function mutations of CFTR protein [3]. Non-classic forms of CF have been associated with mutations that reduce but do not eliminate the function of the CFTR protein [4].
F508del CFTR gene mutation in patients with allergic bronchopulmonary aspergillosis
Published in Journal of Asthma, 2018
Maria N. Gamaletsou, Gemma Hayes, Chris Harris, Joanna Brock, Eavan G. Muldoon, David W. Denning
The following retrospective data were collected from the medical records of each individual within the final cohort. Data were divided into demographic details (age and gender); diagnosis (primary diagnosis and associated co-morbidities for example bronchiectasis, asthma, and sinusitis); immunological and serological biomarkers; mannose binding lectin (MBL), total IgE, serum immunoglobulins, Aspergillus IgG, Aspergillus IgE, C-reactive protein (CRP), Haemophilus influenza, and Pneumococcal serology; measures of pulmonary function and associated limitation via the Medical Research Council (MRC) dyspnea score, as well as forced expiratory volume in the first second (FEV1). The result of CF genotyping was evaluated, looking specifically for the presence of the delta F508 mutation.