Meconium ileus
Mark Davenport, James D. Geiger, Nigel J. Hall, Steven S. Rothenberg in Operative Pediatric Surgery, 2020
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.
Disorders of the respiratory system
Judy Bothamley, Maureen Boyle in Medical Conditions Affecting Pregnancy and Childbirth, 2020
Those who are carriers of cystic fibrosis have one faulty gene and one functioning gene and therefore they can produce the vital salt-transporting gene and do not suffer the symptoms of cystic fibrosis. Most people will be unaware that they carry the faulty gene, although they may seek genetic testing if they have a family history of cystic fibrosis. However, finding the faulty mutation is not entirely straightforward. The most common mutation (found in 75% of people) that affects the CFTR gene is called the delta F508 mutation. However, there are over 1200 places along the CFTR gene that have been identified as areas of change that can impact upon the function of the gene, making it difficult to test for all these changes. Testing is carried out on the 30 most common points, including delta F508 and yields approximately 90% of mutations. Testing can be more accurate when the mutation has been identified in an index case (a relative of the person being tested with cystic fibrosis) (Turner, et al., 2005).
Disorders of the respiratory system
Judy Bothamley, Maureen Boyle in Medical Conditions Affecting Pregnancy and Childbirth, 2020
CF is an autosomal recessive inherited condition. Those who are carriers of cystic fibrosis have one faulty gene and one functioning gene and therefore they can produce the vital salt-transporting gene and do not suffer the symptoms of cystic fibrosis. Most people will be unaware that they carry the faulty gene, although they may seek genetic testing if they have a family history of cystic fibrosis. However, finding the faulty mutation is not entirely straightforward. The most common mutation (found in 75% of people), that affects the CFTR gene, is called the delta F508 mutation. However, the number of identified CFTR mutations now exceeds 1,90038 and there are over 1,200 places along the CFTR gene that have been identified as areas of change that can impact upon the function of the gene, making it difficult to test for all these changes. Testing is carried out on the 30 most common points, including delta F508, and yields approximately 90% of mutations. Testing can be more accurate when the mutation has been identified in an index case (a relative with cystic fibrosis of the person being tested) and needs to consider the common mutations in the specific ethnic background38.
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.
Inherited causes of exocrine pancreatic insufficiency in pediatric patients: clinical presentation and laboratory testing
Published in Critical Reviews in Clinical Laboratory Sciences, 2023
Tatiana N. Yuzyuk, Heather A. Nelson, Lisa M. Johnson
Cystic fibrosis (CF) is the most common autosomal recessive disorder, with an estimated prevalence of 1/3,000 in Caucasians. However, this progressive disorder can affect people of every racial and ethnic group. According to the most recent Cystic Fibrosis Foundation Patient Registry data, almost 40,000 children and adults are currently living with CF in the United States [2]; worldwide, this number reaches 162,428 people across 94 countries [3]. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, in which more than 1,700 disease-causing variants have been identified [2]. The gene encodes a phosphorylation-regulated channel responsible for chloride and bicarbonate transport across the apical surface of epithelial cells, which is important in multiple organs including the lungs, sweat glands, gastrointestinal tract, vas deferens, and pancreas [4]. The impaired function of the CFTR protein causes a multisystemic disorder, but deterioration of pulmonary function leading to respiratory failure is the leading cause of morbidity and mortality in CF. Within the pancreas, insufficient ions and fluid secretions cause the accumulation of thick mucus in the ductal cells, which progressively leads to obstruction and acinar injury. The overall effects on the pancreas are systemic inflammation, fatty infiltration, fibrosis, and eventually, complete loss of exocrine function [5]. The endocrine pancreatic function is also compromised due to progressive damage to islet cells leading to the development of CF-related diabetes (reviewed in [6]).
Related Knowledge Centers
- Bicarbonate
- Chloride
- Epithelium
- Membrane Protein
- Mucus
- Cystic Fibrosis
- Cell Membrane
- Ion Channel
- Gene
- Atp-Binding Cassette Transporter