scholarly journals The Novel CFTR Mutation A457P in a Male with a Delayed Diagnosis of Cystic Fibrosis

2011 ◽  
Vol 2011 ◽  
pp. 1-4
Author(s):  
Kate H. Cole ◽  
Patrick R. Sosnay ◽  
Lonny B. Yarmus ◽  
Jonathan B. Zuckerman
Keyword(s):  
Cystic Fibrosis ◽  
Genetic Testing ◽  
Delayed Diagnosis ◽  
Late Complications ◽  
Transmembrane Conductance Regulator ◽  
The Novel ◽  
Transmembrane Conductance ◽  
Respiratory Compromise ◽  
Mild Phenotype ◽  
Cystic Fibrosis Transmembrane

Cystic fibrosis (CF) is an autosomal recessive disease that may be caused by more than 1000 different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We describe the case of a CF patient who was initially diagnosed at 16 years of age after presenting with mild respiratory compromise and pancreatic sufficiency. When genetic testing was first performed using a CF mutation panel, only a single F508del CFTR allele was identified. We subsequently performed testing, which revealed a previously unreported mutation: A457P (p.Ala457Pro, c.1369G>C). The patient's clinical course through adulthood is described, and genotype-phenotype correlation is discussed. The A457P mutation appears to confer a relatively mild phenotype, as is usually observed with CFTR class IV–VI defects. With the advent of more comprehensive and widely available genetic testing techniques, identification of CF genotypes in patients with milder disease variants may help stratify patients for targeted therapy and prevent late complications of the disease.

scholarly journals Motion-Genetic Testing is Useful in the Diagnosis of Nonhereditary Pancreatic Conditions: Arguments Against the Motion

2003 ◽  
Vol 17 (1) ◽  
pp. 53-55 ◽  
Author(s):  
Jonathan A Cohn
Keyword(s):  
Cystic Fibrosis ◽  
Genetic Testing ◽  
Gene Interactions ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Lung Disease ◽  
Increased Risk ◽  
Idiopathic Chronic Pancreatitis ◽  
Cystic Fibrosis Transmembrane ◽  
Compound Heterozygotes

Mutations of two genes, the cystic fibrosis transmembrane conductance regulator gene (CFTR) and the pancreatic secretory trypsin inhibitor gene (PSTI), are associated with an increase in the risk of idiopathic chronic pancreatitis. Persons who have mutations of bothCFTRalleles (one severely and one mildly affected) are especially susceptible to this disease. Because these compound heterozygotes have sufficient residualCFTRfunction, they do not develop cystic fibrosis lung disease. OnePSTImutation, N34S, independently increases the risk of pancreatitis. Thus, the risk of pancreatitis is greatest among individuals who areCFTRcompound heterozygotes and who also have thePSTImutation. Nonetheless, most people withCFTRandPSTImutations do not develop pancreatitis. This fact indicates that environmental influences and gene-gene interactions also affect pancreatitis risk. AlthoughCFTRandPSTIgenetic testing can identify persons at an increased risk of pancreatitis, there are several reasons why the routine screening of individuals with nonhereditary pancreatitis is not recommended at this time: most disease-associated mutations are not detected by readily available techniques, genetic counselling guidelines do not exist, most patients with mutations do not develop pancreatitis and the results of testing do not affect the clinical management of pancreatitis.

scholarly journals Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy: A Review for the Otolaryngologist

2020 ◽  
Vol 34 (4) ◽  
pp. 573-580
Author(s):  
Saangyoung E. Lee ◽  
Zainab Farzal ◽  
M.Leigh Anne Daniels ◽  
Brian D. Thorp ◽  
Adam M. Zanation ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Respiratory Compromise ◽  
Basic Understanding ◽  
Epithelial Cultures ◽  
Cf Transmembrane Conductance Regulator ◽  
Cystic Fibrosis Transmembrane ◽  
Cftr Modulators ◽  
Initial Results

Background Cystic fibrosis (CF) is a genetic disease that may result in multiple systemic disorders and potentially fatal severe respiratory compromise. However, the advent of CF transmembrane conductance regulator (CFTR) modulators has changed the management of CF for patients with select mutations. Although clinical trials have highlighted increased pulmonary function and decreased exacerbations as a result of these novel therapies, their effect on the sinuses has not been well-described. Objective Our objective is to review the CFTR modulators to provide otolaryngologists, physicians who frequently care for patients with CF, a basic understanding of these drugs and their effects on chronic rhinosinusitis (CRS) in patients with CF. Methods The clinically approved and available CFTR modulators and specific indications for their use are reviewed. Additionally, a systematic review of these therapies and effects on CRS in CF was performed. Results Four Food and Drug Administration approved CFTR modulators are available for patients with CF. Current drugs are approved for gating, residual function, or F508del mutations. Multiple reports describe CFTR modulators’ increase in transepithelial ion transport in nasal epithelial cultures; however, clinical studies regarding effects of these modulators on sinonasal health are limited to 5 studies that present new data of the effects of CFTR modulators in CRS. Conclusions CFTR modulators have changed management of CF. Initial studies of these medications demonstrate promising results in CF; however, there is a paucity of literature describing the effect of CFTR modulators on CF-associated CRS, although initial results are encouraging.

Cystic fibrosis transmembrane conductance regulator (CFTR) activity in nasal epithelial cells from cystic fibrosis patients with severe genotypes

2002 ◽  
Vol 103 (4) ◽  
pp. 417-424 ◽  
Author(s):  
C. ANDERSSON ◽  
A. DRAGOMIR ◽  
L. HJELTE ◽  
G.M. ROOMANS
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Chloride Transport ◽  
Essential Fatty Acids ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Mild Phenotype ◽  
Nasal Epithelial Cells ◽  
Function Number ◽  
Cystic Fibrosis Transmembrane

Cystic fibrosis is a heterogenic disease, in which the phenotype can also vary for patients with the same genotype. In the present study the function of the cystic fibrosis transmembrane conductance regulator (CFTR) in nasal epithelial cells from 19 adult patients with cystic fibrosis was investigated. All patients had severe mutations, whereby no or little functional CFTR is expected in the plasma membrane. Of the patients, 15 were homozygous for ΔF508-CFTR (i.e. CTFR lacking residue Phe-508). The others were ΔF508-heterozygous with 3659delC, 394delTT or 2183AA→G. Nasal epithelial cells, obtained by nasal brushings, were loaded with the fluorescent probe N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide to measure Cl- efflux. In most of the cystic fibrosis patients, forskolin plus isobutylmethylxanthine was unable to elicit any response. Unexpectedly, cells from three cystic fibrosis patients (two ΔF508/ΔF508 patients and one ΔF508/3659delC patient) responded to stimulation in a wild-type manner. It was investigated whether this residual chloride transport function was associated with a milder phenotype. Clinical parameters studied were lung function, number of antibiotic courses, Shwachman score, Bhalla score, age at chronic colonization with Pseudomonas aeruginosa and the pattern of essential fatty acids in serum phospholipids. Unknown factors may affect the presence of functional CFTR in patients with severe CFTR mutations. However, we could not find a correlation between the response to cAMP and any of the phenotype parameters. It appears that functional cAMP transport in the nasal epithelium is no guarantee of a mild phenotype and, conversely, that a patient lacking cAMP-dependent chloride transport can develop a mild phenotype.

scholarly journals A novel procedure for the efficient purification of the cystic fibrosis transmembrane conductance regulator (CFTR)

1997 ◽  
Vol 327 (1) ◽  
pp. 17-21 ◽  
Author(s):  
Mohabir RAMJEESINGH ◽  
Canhui LI ◽  
Elizabeth GARAMI ◽  
Ling-Jun HUAN ◽  
Marek HEWRYK ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Chloride Channel ◽  
Single Step ◽  
High Yield ◽  
Sf9 Cells ◽  
Transmembrane Conductance Regulator ◽  
The Novel ◽  
Transmembrane Conductance ◽  
Metal Affinity ◽  
Cystic Fibrosis Transmembrane

This report describes a novel, single-step strategy for the purification of the cystic fibrosis transmembrane conductance regulator from Sf9 cells, which will facilitate studies of the structure–function relationships of this clinically important molecule. The new method combines the use of the novel detergent sodium pentadecafluoro-octanoate with metal-affinity chromatography to produce a high yield of purified protein which can be functionally reconstituted as a chloride channel and an ATPase.

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