Decades of cough: delayed recognition of atypical cystic fibrosis in an adult patient

The new edition of the synopsis remains the only textbook on pathology concise enough to be taken in one's pocket and yet complete enough to provide some valuable information and a good reference on many subjects. This book will certainly be useful for the busy practitioner trying to refresh hazy memories on general pathology and problems of the adult patient. The information available on problems of specific interest to the pediatrician is, as could be expected in such an abridged text, scant and sketchy. There are, however, excellent "concentrated" descriptions of some pediatric conditions, e.g., cystic fibrosis of the pancreas; problems of current interest are mentioned, such as pneumocystis pneumonia and measles pneumonia.

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Urinary Retention Due to Severe Pseudocystic Mucoid Degeneration of the Prostatic Matrix: A Rare Urologic Manifestation of Cystic Fibrosis

Urologia Internationalis ◽

10.1159/000368911 ◽

2015 ◽

Vol 95 (4) ◽

pp. 486-488

Author(s):

Gesa Kellermann ◽

Aristotelis G. Anastasiadis ◽

Desirée L. Dräger ◽

Friedrich Prall ◽

Oliver W. Hakenberg

Keyword(s):

Cystic Fibrosis ◽

Urinary Retention ◽

Genetic Disease ◽

Autosomal Recessive ◽

Structural Changes ◽

Histopathological Examination ◽

Underlying Disease ◽

Exocrine Glands ◽

Mucoid Degeneration ◽

Prostatic Enlargement

Cystic fibrosis (CF) is an autosomal recessive genetic disease, which is characterized by the production of thick mucus in exocrine glands. The main cause for morbidity and mortality in CF patients is respiratory failure. The gastrointestinal system is also commonly affected. Urologic manifestations of CF include infertility and azoospermia, nephrolithiasis, and stress urinary incontinence. In this report, we describe a 33-year-old male, who presented with recurrent urinary retention due to prostatic enlargement despite his young age. After transurethral resection, the voiding problems resolved. Histopathological examination, however, revealed a severe pseudocystic mucoid degeneration of the prostatic matrix as a cause of his subvesical obstruction. Although these structural changes are most probably due to his underlying disease, detailed histologic features have not been described in the literature.

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Cystic fibrosis: A cell culture study on an adult patient population*

Clinical Genetics ◽

10.1111/j.1399-0004.1976.tb01607.x ◽

2008 ◽

Vol 9 (5) ◽

pp. 527-532 ◽

Cited By ~ 3

Author(s):

B. Shannon Danes ◽

Margaret E. Hodson ◽

J. Batten

Keyword(s):

Cystic Fibrosis ◽

Cell Culture ◽

Adult Patient ◽

Patient Population ◽

Culture Study ◽

Cell Culture Study ◽

A Cell

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Stenotrophomonas maltophilia phenotypic and genotypic features through 4-year cystic fibrosis lung colonization

Journal of Medical Microbiology ◽

10.1099/jmm.0.001281 ◽

2020 ◽

Author(s):

Eliana Alcaraz ◽

Daniela Centrón ◽

Gabriela Camicia ◽

María Paula Quiroga ◽

José Di Conza ◽

...

Keyword(s):

Cystic Fibrosis ◽

Adult Patient ◽

Virulence Factors ◽

Stenotrophomonas Maltophilia ◽

Type Species ◽

Mutation Frequency ◽

Content Type ◽

Link Type ◽

Clonal Relatedness ◽

Over Time

Introduction. Stenotrophomonas maltophilia has emerged as one of the most common multi-drug-resistant pathogens isolated from people with cystic fibrosis (CF). However, its adaptation over time to CF lungs has not been fully established. Hypothesis. Sequential isolates of S. maltophilia from a Brazilian adult patient are clonally related and show a pattern of adaptation by loss of virulence factors. Aim. To investigate antimicrobial susceptibility, clonal relatedness, mutation frequency, quorum sensing (QS) and selected virulence factors in sequential S. maltophilia isolates from a Brazilian adult patient attending a CF referral centre in Buenos Aires, Argentina, between May 2014 and May 2018. Methodology. The antibiotic resistance of 11 S. maltophilia isolates recovered from expectorations of an adult female with CF was determined. Clonal relatedness, mutation frequency, QS variants (RpfC–RpfF), QS autoinducer (DSF) and virulence factors were investigated in eight viable isolates. Results. Seven S. maltophilia isolates were resistant to trimethoprim–sulfamethoxazole and five to levofloxacin. All isolates were susceptible to minocycline. Strong, weak and normomutators were detected, with a tendency to decreased mutation rate over time. XbaI PFGE revealed that seven isolates belong to two related clones. All isolates were RpfC–RpfF1 variants and DSF producers. Only two isolates produced weak biofilms, but none displayed swimming or twitching motility. Four isolates showed proteolytic activity and amplified stmPr1 and stmPr2 genes. Only the first three isolates were siderophore producers. Four isolates showed high resistance to oxidative stress, while the last four showed moderate resistance. Conclusion. The present study shows the long-time persistence of two related S. maltophilia clones in an adult female with CF. During the adaptation of the prevalent clones to the CF lungs over time, we identified a gradual loss of virulence factors that could be associated with the high amounts of DSF produced by the evolved isolates. Further, a decreased mutation rate was observed in the late isolates. The role of all these adaptations over time remains to be elucidated from a clinical perspective, probably focusing on the damage they can cause to CF lungs.

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Complex Genetic Diseases

Genomics and Personalized Medicine ◽

10.1093/wentk/9780190234775.003.0006 ◽

2016 ◽

Author(s):

Michael Snyder

Keyword(s):

Cystic Fibrosis ◽

Genetic Disease ◽

Single Gene ◽

Genetic Diseases ◽

Gene Variants ◽

Tay Sachs Disease ◽

Causative Effect ◽

Complex Genetic Diseases

What is a complex genetic disease? Although great strides have been made to identify single gene variants that have a strong causative effect for a particular disease (e.g., CFTR mutations for cystic fibrosis and HEXA mutations for Tay-Sachs disease), the...

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Editorial: Special Issue on “Therapeutic Approaches for Cystic Fibrosis”

International Journal of Molecular Sciences ◽

10.3390/ijms21186657 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6657

Author(s):

Nicoletta Pedemonte

Keyword(s):

Cystic Fibrosis ◽

Genetic Disease ◽

Special Issue ◽

Therapeutic Approaches ◽

Editorial Special Issue

Cystic fibrosis (CF) is the most common lethal genetic disease in Caucasian populations, occurring in approximately 1 in 3000 newborns worldwide [...]

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CYSTIC FIBROSIS – A GUIDE FOR CLINICIANS IN REPRODUCTIVE AND OBSTETRIC MEDICINE

Fetal and Maternal Medicine Review ◽

10.1017/s0965539509990180 ◽

2010 ◽

Vol 21 (1) ◽

pp. 36-54 ◽

Cited By ~ 5

Author(s):

FRANK P EDENBOROUGH ◽

ALISON M MORTON

Keyword(s):

Cystic Fibrosis ◽

Early Childhood ◽

Young People ◽

Genetic Disease ◽

Female Reproduction ◽

Paper Briefly ◽

Common Life ◽

European Guidelines ◽

Obstetric Medicine ◽

The Uk

Cystic Fibrosis (CF) is the most common life-shortening recessive genetic disease in the UK. Far from being a condition managed exclusively by paediatricians with sufferers dying in early childhood, CF is now a condition in which adults outnumber children with the condition, and the death of a child in a paediatric centre is rare. As increasing numbers of young people grow up relatively healthy it is unsurprising they begin to ask about relationships, sex, fertility and the possibility of having a child. This paper briefly describes the genetics, pathophysiology and clinical features of CF with an emphasis on how it pertains to female reproduction. The management of women with CF considering having a baby including contraception, preparation for pregnancy, the pregnancy itself, delivery and the post natal period will be discussed. Contraindications to pregnancy, method of termination, and pregnancy after transplantation will also be considered. Much of the detailed management is given in the European Guidelines for the Management of Pregnancy in Women with CF on which this paper is based.

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95 Invitro correction of F508del and G542X mutations in sheep fibroblasts of cystic fibrosis models

Reproduction Fertility and Development ◽

10.1071/rdv33n2ab95 ◽

2021 ◽

Vol 33 (2) ◽

pp. 155

Author(s):

K. Bunch ◽

I. V. Perisse ◽

Z. Fan ◽

K. White ◽

I. Polejaeva

Keyword(s):

Cystic Fibrosis ◽

Genetic Disease ◽

The United States ◽

Human Genetic Disease ◽

Nonsense Mediated Decay ◽

Homology Directed Repair ◽

Mutant Transcript ◽

Pcr Products ◽

Exon 11 ◽

Cf Transmembrane Conductance Regulator

Cystic fibrosis (CF) is a human genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Among the ∼2000 known CF mutations, the F508del mutation is found in 84% and G542X in 4.6% of the CF patients in the United States. The F508del mutation occurs in exon 11 and is characterised by deletion of the “CTT” nucleotides, resulting in deletion on the phenylalanine residue at the position 508 of CFTR. This causes misfolding of the CFTR protein, which is further degraded by proteases. The G542X mutation is a nonsense mutation found in exon 12 and associated with nonsense-mediated decay of the mutant transcript causing the absence of protein production. Previously, we generated CFTRF508del/F508del and CFTRG542X/G542X lambs (unpublished) using CRISPR/Cas9 and somatic cell nuclear transfer (SCNT) techniques. We hypothesised that gene editing may be an effective tool to correct these mutations and permanently cure this genetic disease. Thus, in this study, we evaluated the efficiency of CRISPR/Cas9-meditated gene knock-in to correct the F508del and G542X mutations in sheep fibroblasts invitro. We designed single guide (sg)RNAs using the Benchling software (https://benchling.com/academic) and approximately 100bp of single-stranded oligodeoxynucleotides (ssODNs) targeting the mutation sites at exon 11 and 12 to introduce either “CTT” or change the “T” to “G” nucleotide in genome of F508del or G542X CF sheep cells, respectively. Each of Cas9/sgRNA ribonucleoproteins was transfected into sheep fibroblast cells along with ssODNs using the Lonza-4D-NucleofectorTM (Lonza) system for homology-directed repair. The transfected cells were subsequently cultured in Dulbecco’s modified Eagle medium, supplemented with 15% fetal bovine serum and 1% penicillin, and incubated at 38.5°C. DNA was extracted 48h post-transfection to validate mutation efficiency. PCR products of the exons 11 and 12 were ligated into T-vector, and bacterial colonies were selected based on blue/white screening. In total, we isolated 32 single cell bacterial colonies for each mutant. Sequencing results indicate that “CTT” was introduced in 4/26 (15.3%) plasmid colonies, and “T to G” replaced in 13/31 (41.9%) colonies. Therefore, our results indicate that the F508del and G542X mutations can be effectively corrected in CF sheep fibroblasts invitro using a CRISPR/Cas9 approach.

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Association of pancreatic adenocarcinoma, mild lung disease, and delta F508 mutation in a cystic fibrosis patient

Clinical Chemistry ◽

10.1093/clinchem/40.10.1972 ◽

1994 ◽

Vol 40 (10) ◽

pp. 1972-1974 ◽

Cited By ~ 16

Author(s):

G J Tsongalis ◽

G Faber ◽

F G Dalldorf ◽

K J Friedman ◽

L M Silverman ◽

...

Keyword(s):

Cystic Fibrosis ◽

General Population ◽

Lung Disease ◽

Genetic Disease ◽

Obstructive Lung Disease ◽

Malignant Disease ◽

Molecular Data ◽

Cystic Fibrosis Mutation ◽

First Case ◽

Adenocarcinoma Of The Pancreas

Abstract A case of adenocarcinoma of the pancreas and mild lung disease in a 39-year-old man homozygous for the delta F508 cystic fibrosis mutation is presented. Cystic fibrosis is the most common lethal genetic disease in Caucasians, and is most commonly associated with severe obstructive lung disease. To our knowledge, this is only the fifth case of adenocarcinoma of the pancreas in a CF patient to be reported and the first case for which molecular data are available. The rare incidence of this type of malignancy in the general population suggests a possible association of CF with this malignant disease.

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