EVALUATION OF CFTR CHANNEL FUNCTION AND RESPONSES TO MODULATORS FOR CYSTIC FIBROSIS PATIENTS WITH GENETIC VARIANT F508DEL

2020 ◽  
pp. 232-234
Author(s):  
A. Efremova ◽  
T. Bukharova ◽  
N. Petrova ◽  
N.Kashirskaya Kashirskaya ◽  
Y. Melyanovskaya ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Autosomal Recessive ◽  
Genetic Variant ◽  
Autosomal Recessive Disease ◽  
Target Therapy ◽  
Allelic Frequency ◽  
Common Life ◽  
Life Threatening ◽  
Cftr Protein ◽  
The Russian Federation

Cystic fibrosis (CF) is the most common life-threatening autosomal recessive disease. CF is caused by mutations in the CFTR gene that encodes an anionic channel, which is expressed in epithelial cells. The most common genetic variant is F508del, its allelic frequency in the Russian Federation 52.81% (2017). This variant belongs to class II, leads to incorrect folding of the CFTR protein and its premature degradation. Currently, the effectiveness of target therapy can be individually evaluated by forskolin-induced swelling (FIS) assay on intestinal organoids obtained from CF patients with different genotypes.

How to perform and interpret the sweat test

2019 ◽  
Vol 105 (4) ◽  
pp. 230-235 ◽  
Author(s):  
Anthony Brown ◽  
Laura Jenkins ◽  
Alastair Reid ◽  
Anne Leavy ◽  
Glen McDowell ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Screening Programme ◽  
Autosomal Recessive Disease ◽  
Clinical Suspicion ◽  
Sweat Test ◽  
Western World ◽  
Physiological Basis ◽  
Common Life ◽  
Sweat Testing ◽  
Life Threatening

Cystic fibrosis (CF) is the most common life-threatening autosomal-recessive disease affecting Caucasians in the western world. The sweat test is the main diagnostic test for CF. It is indicated as part of the clinical assessment for infants that have picked up on the national neonatal screening programme. It may also be requested where clinical suspicion of a diagnosis of CF exists despite normal screening results. This article outlines the physiological basis behind sweat testing and the technical aspects of performing the test. Indications for performing the test are also considered. The article aims to provide clinicians with a guide to interpretation of results.

scholarly journals The Future of CRISPR: Looking at Gene Editing as a Treatment For Cystic Fibrosis

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Harisha Kosanam ◽  
Ananya Udyaver ◽  
Waliya Muhammad
Keyword(s):  
Cystic Fibrosis ◽  
Autosomal Recessive ◽  
Gene Editing ◽  
Autosomal Recessive Disease ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Internal Organs ◽  
Cftr Protein ◽  
Cystic Fibrosis Transmembrane ◽  
Cftr Modulators

Cystic Fibrosis (CF) is a genetically inherited chronic disease that causes the production of a thick and sticky mucus primarily in the lungs. The condition tends to become worse over time. Clogged lungs and other internal organs result in breathing issues, susceptibility to infections, digestive problems, and lack of nutrition. CF is an autosomal recessive disease, indicating that an individual must inherit two copies of the defective Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, which then encodes for a malfunctioning CFTR protein. Because of the large number of CF patients that cannot be treated with these CFTR modulators, using gene editing to directly target the mutation can be more effective and efficient in treating cystic fibrosis. In this paper, we will discuss the promises and limitations for using gene editing as a treatment for CF.

PRO–CF–MED, Clinical Proof of concept for a RNA–targeting Oligonucleotide for a Cystic fibrosis–F508del MEDication, Horizon2020

Impact ◽  
2018 ◽  
Vol 2018 (3) ◽  
pp. 52-54
Author(s):  
Nicolas Lamontagne
Keyword(s):  
Cystic Fibrosis ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Rna Targeting ◽  
Threatening Condition ◽  
Life Threatening ◽  
Cftr Protein ◽  
Disease Modifying ◽  
Cystic Fibrosis Transmembrane ◽  
Specific Challenge

Cystic fibrosis (CF) is a progressive life–shortening disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene leading to a dysfunctional CFTR protein. The disease affects over 70,000 patients worldwide and while many mutations are known, the F508del mutation affects 90% of all patients. The absence of CFTR in the plasma membrane leads to a dramatic decrease in chloride efflux, resulting in viscous mucus that causes severe symptoms in vital organs like the lungs and intestines. For CF patients that suffer from the life threatening F508del mutation only palliative treatment exist. PRO–CF–MED addresses the specific challenge of this call by introducing the first disease modifying medication for the treatment of the CF patients with F508del mutation. The PRO–CF–MED project has been designed to assess the potential clinical efficacy of QR–010, an innovative disease modifying oligonucleotide–based treatment for F508del patients. Partners within PRO–CF–MED have generated very promising preclinical evidence for QR–010 which allows for further clinical assessment of QR–010 in clinical trials. PRO–CF–MED will enable the fast translation of QR–010 towards clinical practice and market authorisation. PRO–CF–MED has the potential to transform this life–threatening condition into a manageable one.

scholarly journals Therapeutic guidelines for the treatment of cystic fibrosis

Pharmacia ◽  
2021 ◽  
Vol 68 (1) ◽  
pp. 151-154
Author(s):  
Maria Becheva ◽  
Petar Atanasov
Keyword(s):  
Cystic Fibrosis ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Clinical Evaluations ◽  
Number Of Patients ◽  
Therapeutic Guidelines ◽  
Therapeutic Measures ◽  
One Year ◽  
Respiratory Rehabilitation

Cystic fibrosis (CF) is a complex, systemic autosomal recessive disease that affects the functions of the respiratory system, the digestive tract and all exocrine glands. The frequency for Europe averages 1: 2500 to 1: 3500 live births. The total number of patients with cystic fibrosis in Bulgaria is about 180. About 10% of the patients are diagnosed at birth. About 60–70% of patients are diagnosed before they reach one year of age. Respiratory symptoms predominate in the clinical picture in patients with cystic fibrosis and determine the prognosis in more than 90% of the patients. The treatment of patients with cystic fibrosis is strictly individualized, pharmacological and non-pharmacological and requires a comprehensive therapeutic approach. The complex therapy also includes bronchodilators, NSAIDs, corticosteroids, respiratory rehabilitation in combination with general body massage. Continued courses of broad-spectrum antibiotics are required to suppress chronic infection. With the progression of the disease, complications such as atelectasis, pneumothorax and pulmonary hemorrhages are observed. The establishment of specialized centers with trained and experienced professionals is essential in order to provide optimal patient care. These include frequent clinical evaluations, follow-up of complications, and early interventions for the treatment of patients with cystic fibrosis. The aim of the article is to familiarize the audience with the therapeutic measures applied in the treatment of patients with cystic fibrosis.

21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia

2010 ◽  
Vol 29 (3) ◽  
pp. 191-196 ◽  
Author(s):  
Amy Shaw
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Adrenal Hyperplasia ◽  
Hydroxylase Deficiency ◽  
Enzyme Defect ◽  
The People ◽  
Life Threatening ◽  
Males And Females ◽  
21 Hydroxylase Deficiency ◽  
Autosomal Recessive Pattern

CONONGENITAL ADRENAL hyperplasia (CAH) is an inborn error of metabolism that can produce life-threatening disease in the first one to three weeks of life, unless properly diagnosed and managed. This autosomal recessive disease results in insufficient biosynthesis of cortisol due to an enzyme defect in the adrenal gland. CAH due to 21-hydroxylase (21-OH) deficiency is found in 1/11,000–1/15,000 people in the general population, with a prevalence as high as 1/750 people in some populations such as the Yupik Eskimos in Alaska and the people of La Réunion in France.1 Males and females are equally affected by this disease due to the autosomal recessive pattern of inheritance.

scholarly journals ASTHMA IN CYSTIC FIBROSIS

2015 ◽  
Vol 64 (2) ◽  
pp. 118-121
Author(s):  
Marcela Daniela Ionescu ◽  
◽  
Ioana-Alina Anca ◽  
Mihaela Balgradean ◽  
◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Airway Obstruction ◽  
Autosomal Recessive ◽  
Pulmonary Infection ◽  
Autosomal Recessive Disease ◽  
Personal History ◽  
Common Symptom ◽  
Infection And Inflammation ◽  
History Of

Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians. Lung disease is characterized by impaired mucocilliary clearance with airway obstruction and chronic pulmonary infection and inflammation. Wheeze is a common symptom in CF, but in some cases the wheeze is due to the presence of concomitant asthma. There is no consensus on how to define CF asthma, but the diagnosis is predominantly based on the patient’s strong family and personal history of atopy.

scholarly journals Intracranial Calcifications in Autoimmune Polyendocrine Ectodermal Dystrophy Syndrome (APECED): About A Case Report

2021 ◽  
pp. 1-3
Author(s):  
Benfaddoul O ◽  
◽  
Zouita B ◽  
El azzouzi B ◽  
Basraoui N ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Chronic Mucocutaneous Candidiasis ◽  
Type I ◽  
Syndrome Type ◽  
Autoimmune Polyglandular Syndrome ◽  
Mucocutaneous Candidiasis ◽  
Autoimmune Polyendocrinopathy ◽  
Life Threatening ◽  
Autoimmune Polyglandular Syndrome Type

Autoimmune polyendocrinopathy ectodermal dystrophy (APECED), also known as autoimmune polyglandular syndrome type I (APS I), is an uncommon, but debilitating autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE), It is characterized by a broad and diverse clinical spectrum which can lead to severe metabolic alterations and eventually life-threatening events. Hypoparathyroidism is one of the major criteria for clinical diagnosis, in addition to chronic mucocutaneous candidiasis and autoimmune adrenal insufficiency. This component is responsible for the forming of brain calcifications which tend to have a characteristic predilection for the basal ganglia. In this article, we report an additional case to the literature and provide a literature review of the expanding radiological spectrum of this syndrome

Cystic fibrosis

2021 ◽  
pp. 285-298
Author(s):  
Terry Robinson ◽  
Jane Scullion
Keyword(s):  
Cystic Fibrosis ◽  
High Risk ◽  
Infection Control ◽  
Western World ◽  
Life Care ◽  
Inherited Disease ◽  
Adult Care ◽  
Common Life ◽  
Clinical Presentations ◽  
Life Threatening

Cystic fibrosis (CF) is the most common, life-threatening, and recessively inherited disease in the Western world. This chapter provides an overview of the condition, including its aetiology, pathology, and genetics. It then covers the clinical presentations and confirmation of diagnosis of CF, complications (respiratory, gastrointestinal, pancreatic, bowel, hepatic, reproductive, and diabetic). Anyone recognized as having high risk of having a baby with CF and in whom pregnancy is contemplated, or who has a newborn with CF, should be offered screening and early genetic advice. Care and management are described in detail, including nutrition, physiotherapy, infection control, antibiotics, the transition from paediatric to adult care, transplant, and end-of-life care.

scholarly journals Cystic fibrosis-related diabetes: an update

QJM ◽  
2020 ◽  
Author(s):  
F Frost ◽  
M J Walshaw ◽  
D Nazareth
Keyword(s):  
Cystic Fibrosis ◽  
Life Expectancy ◽  
Early Mortality ◽  
Transmembrane Conductance Regulator ◽  
Regulator Gene ◽  
Transmembrane Conductance ◽  
Common Life ◽  
Life Threatening ◽  
Underlying Mechanisms ◽  
Cf Transmembrane Conductance Regulator

Summary Cystic fibrosis (CF) is the most common life-threatening inherited condition in the Caucasian population, where mutations in the CF transmembrane conductance regulator gene result in a multifactorial syndrome, with pulmonary disease representing the largest contributor to morbidity and mortality. Life expectancy has improved and the recent development of disease-modifying CF transmembrane conductance regulator modulator therapies is likely to further improve survival. However, increasing life expectancy brings new challenges related to the complications of a chronic disease including an increasing prevalence of CF-related diabetes, itself associated with increased morbidity and early mortality. This review provides an update as regards the underlying mechanisms, investigation and management of CF-related diabetes.

scholarly journals Mucus Distribution Model in a Lung with Cystic Fibrosis

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Sara Zarei ◽  
Ali Mirtar ◽  
Forest Rohwer ◽  
Douglas J. Conrad ◽  
Rebecca J. Theilmann ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Volume Growth ◽  
Early Mortality ◽  
Distribution Model ◽  
Construction Process ◽  
Airway Wall ◽  
Single Patient ◽  
Live Births

Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians with a reported incidence of 1 in every 3200 live births. Most strikingly, CF is associated with early mortality. Host in flammatory responses result in airway mucus plugging, airway wall edema, and eventual destruction of airway wall support structure. Despite aggressive treatment, the median age of survival is approximately 38 years. This work is the first attempt to parameterize the distributions of mucus in a CF lung as a function of time. By default, the model makes arbitrary choices at each stage of the construction process, whereby the simplest choice is made. The model is sophisticated enough to fit the average CF patients' spirometric data over time and to identify several interesting parameters: probability of colonization, mucus volume growth rate, and scarring rate. Extensions of the model appropriate for describing the dynamics of single patient MRI data are also discussed.

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