Cystic fibrosis-associated liver disease

2011 ◽  
Author(s):  
R. Mark Beattie ◽  
Anil Dhawan ◽  
John W.L. Puntis
Keyword(s):  
Cystic Fibrosis ◽  
Liver Disease ◽  
Autosomal Recessive ◽  
Biliary Cirrhosis ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Gene Coding ◽  
Severe Cirrhosis ◽  
Cystic Fibrosis Transmembrane ◽  
Biochemical Abnormalities

Pathophysiology 162Clinical features 162Diagnosis 163Management 164Cystic fibrosis (CF) is an autosomal recessive disease resulting from mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) (see Chapter 21). CFTR functions as a transmembrane chloride channel in the apical membrane of most secretory epithelia and the disease thus affects lungs, pancreas, exocrine glands, gut, and liver. In CF-associated liver disease the biliary tract is most commonly involved in a spectrum from asymptomatic to biliary cirrhosis. The liver disease runs from mild and subclinical to severe cirrhosis and portal hypertension. Clinical disease is seen in 4–6% of cases, but there are biochemical abnormalities in 20–50%. At autopsy, fibrosis is present in 20% and steatosis in 50%....

scholarly journals Specialized Pro-Resolving Lipid Mediators in Cystic Fibrosis

2018 ◽  
Vol 19 (10) ◽  
pp. 2865 ◽  
Author(s):  
Réginald Philippe ◽  
Valerie Urbach
Keyword(s):  
Cystic Fibrosis ◽  
Structural Damage ◽  
Bacterial Colonization ◽  
Airway Disease ◽  
Lipid Mediators ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Persistent Inflammation ◽  
Gene Coding ◽  
Cystic Fibrosis Transmembrane

In cystic fibrosis (CF), impaired airway surface hydration (ASL) and mucociliary clearance that promote chronic bacterial colonization, persistent inflammation, and progressive structural damage to the airway wall architecture are typically explained by ion transport abnormalities related to the mutation of the gene coding for the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel. However, the progressive and unrelenting inflammation of the CF airway begins early in life, becomes persistent, and is excessive relative to the bacterial burden. Intrinsic abnormalities of the inflammatory response in cystic fibrosis have been suggested but the mechanisms involved remain poorly understood. This review aims to give an overview of the recent advances in the understanding of the defective resolution of inflammation in CF including the abnormal production of specialized pro-resolving lipid mediators (lipoxin and resolvin) and their impact on the pathogenesis of the CF airway disease.

scholarly journals Molecular analysis of CFTR gene mutations among Iraqi cystic fibrosis patients

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Asal Gailan Abdul-Qadir ◽  
Bassam Musa Al-Musawi ◽  
Rabab Farhan Thejeal ◽  
Saad Abdul-Baqi Al-Omar
Keyword(s):  
Cystic Fibrosis ◽  
Molecular Analysis ◽  
Autosomal Recessive ◽  
Gene Mutations ◽  
Regional Studies ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Multisystem Disease ◽  
Polymorphic Variants ◽  
Cystic Fibrosis Transmembrane

Abstract Background Cystic fibrosis (CF) is an autosomal recessive multisystem disease that results from mutation(s) of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. More than 2100 mutations and polymorphisms have been reported in this gene so far. Incidence and genotyping of CF are under-identified in Iraq. This study aims to determine the types and frequencies of certain CFTR mutations among a sample of Iraqi CF patients. Two groups of patients were included: 31 clinically confirmed CF patients in addition to 47 clinically suspected patients of CF. All confirmed patients had typical, moderate-severe clinical presentation and course of the disease. Molecular analysis was performed on the majority of enrolled patients using the CF-stripAssay® kit supplied by ViennaLab diagnostics, GmbH, Austria. Results The mutation-detection rate from the tested 34 mutations in this study was 19.5% and the 8 detected mutations were as follows: 3120+1G>A and W1282X were found in 3 (4.17%) patients each; F508del and R1162X were found in 2 (2.78%) patients each; 3272-26A>G, R347P, I507del, and 2183AA>G were found in 1 (1.38%) patient each. Polymorphic variants of IVS8, namely 5T, 7T, and 9T, were detected in ~ 70%. These results were nearly similar to what was reported in regional countries. Conclusion Cystic fibrosis seems to be not rare as previously thought. 3120+1G>A and W1282X are the two most commonly detected mutations. F508del needs to be included in all future tests, while the I507del mutation was uniquely reported in this study but not in regional studies.

scholarly journals Cutaneous Manifestations of Cystic Fibrosis

2018 ◽  
Vol 3 (1) ◽  
pp. 39-44
Author(s):  
Anca Chiriac ◽  
Laura Trandafir ◽  
Cristian Podoleanu ◽  
Simona Stolnicu
Keyword(s):  
Cystic Fibrosis ◽  
Autosomal Recessive ◽  
Skin Lesions ◽  
Nutritional Deficiencies ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cutaneous Lesions ◽  
Cutaneous Manifestations ◽  
Cystic Fibrosis Transmembrane

Abstract Cystic fibrosis (CF) is an autosomal recessive affliction triggered by genetic mutations in the cystic fibrosis transmembrane conductance regulator. The lung and pancreas are the most frequently affected organs in cystic fibrosis, cutaneous involvement is undervalued and underdiag-nosed. Skin lesions observed in patients diagnosed with cystic fibrosis are not well known and can create confusions with other dermatological diseases. The diagnosis of cutaneous lesions as signs of cystic fibrosis by pediatricians or dermatologists, despite their overlapping with different nutritional deficiencies, would allow earlier diagnosis and proper treatment and could improve quality of life and outcomes.

scholarly journals Production of CFTR-ΔF508 Rabbits

2021 ◽  
Vol 11 ◽  
Author(s):  
Dongshan Yang ◽  
Xiubin Liang ◽  
Brooke Pallas ◽  
Mark Hoenerhoff ◽  
Zhuoying Ren ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Autosomal Recessive ◽  
Common Mutation ◽  
Transmembrane Conductance Regulator ◽  
Germline Transmission ◽  
Transmembrane Conductance ◽  
Gene Encoding ◽  
Cystic Fibrosis Transmembrane ◽  
Phenylalanine Residue ◽  
F1 Generation

Cystic Fibrosis (CF) is a lethal autosomal recessive disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation is the deletion of phenylalanine residue at position 508 (ΔF508). Here we report the production of CFTR-ΔF508 rabbits by CRISPR/Cas9-mediated gene editing. After microinjection and embryo transfer, 77 kits were born, of which five carried the ΔF508 mutation. To confirm the germline transmission, one male ΔF508 founder was bred with two wild-type females and produced 16 F1 generation kits, of which six are heterozygous ΔF508/WT animals. Our work adds CFTR-ΔF508 rabbits to the toolbox of CF animal models for biomedical research.

scholarly journals Cystic Fibrosis - Related Diabetes

2021 ◽  
Vol 11 (6) ◽  
pp. 42-46
Author(s):  
Marcin Makuch ◽  
Marcelina Makuch
Keyword(s):  
Cystic Fibrosis ◽  
Autosomal Recessive ◽  
Glucose Tolerance Test ◽  
Autosomal Recessive Disease ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Regulator Protein ◽  
Cystic Fibrosis Transmembrane

Cystic fibrosis (CF) is life-shortening autosomal recessive disease, caused by mutations in the cystic fibrosis transmembrane conductance regulator protein. The most common of CF complications is cystic fibrosis-related diabetes (CFRD). The pathophysiology of CFRD is complex. The best test for screening and diagnosis of CFRD is the oral glucose tolerance test (OGTT). Insulin therapy is a treatment of choice in CFDR pharmacotherapy. An inseparable element of CFRD therapy is also physical activity and diet.

Patient and Family Issues Regarding Genetic Testing for Cystic Fibrosis

2011 ◽  
Vol 29 (1) ◽  
pp. 303-329 ◽  
Author(s):  
Kathleen J. H. Sparbel ◽  
Audrey Tluczek
Keyword(s):  
Cystic Fibrosis ◽  
Autosomal Recessive ◽  
The United States ◽  
National Institutes Of Health ◽  
Electrolyte Imbalance ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Respiratory Involvement ◽  
Family Issues ◽  
Cystic Fibrosis Transmembrane

Cystic fibrosis (CF) is a potentially life-shortening autosomal recessive genetic condition resulting in chronic progressive respiratory involvement, malnutrition, electrolyte imbalance, and male infertility. It is the most common autosomal inherited condition in the White population, and its presence is recorded with varying prevalence across ethnicities. Since the 1989 discovery of the genetic variant F508del, the most common cystic fibrosis transmembrane conductance regulator (CFTR) mutation, more than 1,900 CF mutations have been identifi ed. The 1997 National Institutes of Health (NIH) Consensus Statement on Cystic Fibrosis, along with 2001 and 2005 recommendations from the American College of Obstetricians and Gynecologists (ACOG), provide the basis for population CF carrier screening in the prenatal setting. Recommendations for newborn screening (NBS) for cystic fibrosis were released in 2004, with NBS programs in the United States initiated thereafter.

scholarly journals High-Throughput Screening for Readthrough Modulators of CFTR PTC Mutations

2017 ◽  
Vol 22 (3) ◽  
pp. 315-324 ◽  
Author(s):  
Feng Liang ◽  
Haibo Shang ◽  
Nikole J. Jordan ◽  
Eric Wong ◽  
Dayna Mercadante ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
High Throughput Screening ◽  
Premature Termination Codon ◽  
Surface Expression ◽  
Hereditary Disease ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Gene Coding ◽  
Cystic Fibrosis Transmembrane ◽  
Personalized Medicines

Cystic fibrosis (CF) is a hereditary disease caused by mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). A large number of nearly 2000 reported mutations, including the premature termination codon (PTC) mutations, urgently require new and personalized medicines. We have developed cell-based assays for readthrough modulators of CFTR PTC mutations (or nonsense mutation suppressors), based on the trafficking and surface expression of CFTR. Approximately 85,000 compounds have been screened for two PTC mutations (Y122X and W1282X). The hit rates at the threshold of 50% greater than vehicle response are 2% and 1.4% for CFTR Y122X and CFTR W1282X, respectively. The overlap of the two hit sets at this stringent hit threshold is relatively small. Only ~28% of the hits from the W1282X screen were also hits in the Y122X screen. The overlap increases to ~50% if compounds are included that in the second screen achieve only a less stringent hit criterion, that is, horseradish peroxidase (HRP) activity greater than three standard deviations above the mean of the vehicle. Our data suggest that personalization may not need to address individual genotypes, but that patients with different CFTR PTC mutations could benefit from the same medicines.

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