Article
Pediatrics
Michael J. J. Rock, Mei Baker, Nicholas Antos, Philip M. M. Farrell
Summary: Using next generation sequencing (NGS) in combination with immunoreactive trypsinogen (IRT) can effectively identify infants at risk for cystic fibrosis (CF) without significantly increasing the rate of detecting carriers. NGS has the potential to enhance equity, sensitivity, and detection of more CF patients with 2 variants during the screening process.
PEDIATRIC PULMONOLOGY
(2023)
Review
Genetics & Heredity
Ziga I. Remec, Katarina Trebusak Podkrajsek, Barbka Repic Lampret, Jernej Kovac, Urh Groselj, Tine Tesovnik, Tadej Battelino, Marusa Debeljak
Summary: Newborn screening was introduced in the 1960s, and has expanded over time with the advancement of technology, particularly high-throughput sequencing. Genomic sequencing is now widely used in clinical applications, including newborn screening, but has also raised various concerns and challenges.
FRONTIERS IN GENETICS
(2021)
Review
Biochemistry & Molecular Biology
Evelina Moliteo, Monica Sciacca, Antonino Palmeri, Maria Papale, Sara Manti, Giuseppe Fabio Parisi, Salvatore Leonardi
Summary: There is substantial evidence that patients with cystic fibrosis (CF) have higher oxidative stress levels, which contribute to the progression of chronic lung damage. CF patients exhibit an abnormal proinflammatory environment in their airways even before infection, possibly due to elevated oxidative stress and abnormal lipid metabolism. CFTR deficiency appears to cause a redox imbalance in epithelial cells and extracellular fluids.
Article
Medical Laboratory Technology
Bennett Oh Vic Shum, Carel Jacobus Pretorius, Letitia Min Fen Sng, Ilya Henner, Paulette Barahona, Emre Basar, Jim McGill, Urs Wilgen, Anna Zournazi, Lilian Downie, Natalie Taylor, Liam Cheney, Sylvania Wu, Natalie Angela Twine, Denis Carolin Bauer, Gerald Francis Watts, Akash Navilebasappa, Kishore Rajagopal Kumar, Jacobus Petrus Johannes Ungerer, Glenn Bennett
Summary: The study found that newborn screening can be expanded using targeted gene sequencing (TGS), which is a feasible and cost-effective method. The TGS assay had a high sensitivity (>99%) and specificity (100%) with a turnaround time of 7 to 10 days and a maximum batch size of 1536 samples. This approach can increase the number of conditions screened and improve the effectiveness of newborn screening programs.
CLINICAL CHEMISTRY
(2023)
Article
Biotechnology & Applied Microbiology
Amanda Cambraia, Mario Campos Junior, Veronica Marques Zembrzuski, Ricardo Magrani Junqueira, Pedro Hernan Cabello, Giselda Maria Kalil de Cabello
Summary: This study conducted complete screening of CFTR in patients with cystic fibrosis through next-generation sequencing, leading to molecular diagnosis and identification of possible molecular candidates for genotype-specific treatments.
Review
Biochemistry & Molecular Biology
Caitlyn Harvey, Sinead Weldon, Stuart Elborn, Damian G. Downey, Clifford Taggart
Summary: The advent of CFTR modulators in cystic fibrosis treatment has transformed the management of the disease, shifting it from being a life-limiting condition to one that can be effectively managed. These genotype-specific therapies have shown significant improvements in various clinical endpoints, but their effects on pathogenic burden and airway infection need further exploration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Jia Liu, Allison P. Berg, Yiting Wang, Walailak Jantarajit, Katy J. Sutcliffe, Edward B. Stevens, Lishuang Cao, Marko J. Pregel, David N. Sheppard
Summary: This study investigates the action of a new CFTR potentiator, CP-628006, and compares it with the marketed CFTR potentiator ivacaftor. CP-628006 has distinct effects compared to ivacaftor, suggesting a different mechanism of CFTR potentiation. The emergence of CFTR potentiators with diverse modes of action makes therapy with combinations of potentiators a possibility.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Medicine, General & Internal
Hannah Farley, Sarah Poole, Stephen Chapman, William Flight
Summary: A retrospective single-center cohort study identified 19 adult patients diagnosed with CF, all of whom had a history of chronic respiratory symptoms and the majority of whom had a CFTR genotype considered eligible for CFTR modulator therapy.
POSTGRADUATE MEDICAL JOURNAL
(2022)
Article
Genetics & Heredity
Farra Chantal, Awwad Johnny, Hamadeh Lama, Khoueiry Pierre, Halawi Zeina, Yazbeck Nadine, Daher Rose, Souaid Mirna, Hamdar Layal, Yammine Tony, Yunis Khalid
Summary: Cystic fibrosis is a common genetic disease in Western countries, with this study finding a high carrier rate of 5.5%-7% in newborns in the Middle Eastern Lebanese population. The research highlights the challenges in interpreting CFTR variants in countries with limited ethnic diversity, emphasizing the importance of premarital screening programs for cystic fibrosis.
ANNALS OF HUMAN GENETICS
(2022)
Article
Pediatrics
Bennett O. V. Shum, Glenn Bennett, Akash Navilebasappa, R. Kishore Kumar
Summary: Cystic Fibrosis (CF) is more common in diverse ethnic groups than previously thought, but current molecular diagnostic tools are biased towards the most common CF-causing DNA variants in Caucasians. Full gene sequencing could address racial inequality in CF testing by identifying a wider range of pathogenic variants in non-Caucasians, improving diagnostic accuracy and reducing delays in diagnosis.
Review
Biochemistry & Molecular Biology
Oscar Fonseca, Maria Salome Gomes, Maria Adelina Amorim, Ana Cordeiro Gomes
Summary: Cystic fibrosis, a monogenic disease, has a diverse clinical presentation involving chronic lung infection, inflammation, and reduced bone mass. The underlying mechanisms of reduced bone mass in cystic fibrosis patients are still unclear. This review explores the relationship between CFTR dysfunction and intrinsic bone defects, as well as the impact of the proinflammatory environment and chronic infection on bone mass maintenance in CF patients.
Article
Obstetrics & Gynecology
Elena D'Alcamo, Giuseppe Gullo, Gaspare Cucinella, Antonino Perino, Sofia Burgio, Andrea Etrusco, Veronica Agrigento, Serena Sclafani, Florinda Listi, Aurelio Maggio, Igea Vega, Antonio Simone Lagana, Amerigo Vitagliano, Marco Noventa, Giovanni Buzzaccarini
Summary: A prospective observational study on CF testing with NGS technique was conducted on 360 subjects in an IVF center, revealing proportions of different CF mutations.
CLINICAL AND EXPERIMENTAL OBSTETRICS & GYNECOLOGY
(2022)
Article
Cell Biology
Jie Huang, Jun Liu, Ruiyi Tian, Kevin Liu, Patrick Zhuang, Hannah Tayla Sherman, Christoph Budjan, Michelle Fong, Min-Seo Jeong, Xue-Jun Kong
Summary: This study demonstrates the clinical feasibility and technical implementation of a WGS genetic report for patients with ASD. By using WGS data from six family trios and considering clinical symptoms and literature review, an evidence-based and transparent bioinformatics pipeline and report framework were provided. This method can contribute to a better understanding of ASD pathophysiology, early detection of associated comorbidities, and personalized treatment based on genetic information.
Article
Pharmacology & Pharmacy
L. Clara Mok, Antonio Garcia-Uceda, Matthew N. Cooper, Mariette Kemner Van De Corput, Marleen De Bruijne, Nathalie Feyaerts, Tim Rosenow, Kris De Boeck, Stephen Stick, Harm A. W. M. Tiddens
Summary: Newly developed quantitative CT outcomes designed for CF lung disease can assess structural abnormalities. CFTR modulators have the potential to reduce these abnormalities. This study aimed to investigate the effect of CFTR modulators on the progression of structural lung disease.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Cell Biology
Francesca Saluzzo, Luca Riberi, Barbara Messore, Nicola Ivan Lore, Irene Esposito, Elisabetta Bignamini, Virginia De Rose
Summary: Cystic Fibrosis (CF) is a genetic disease caused by mutations in the CFTR gene, leading to imbalances in the airway microenvironment and increased susceptibility to infections. CFTR modulators have shown promise in improving airway infections, but their long-term effects remain to be fully understood.
