Review
Endocrinology & Metabolism
Anna Papadopoulou, Evangelia Bountouvi
Summary: Noonan, Costello, and Cardio-facio-cutaneous syndromes are RASopathies characterized by overlapping clinical features and abnormalities in the Ras/MAPK signaling pathway. Skeletal dysmorphisms, including chest wall anomalies, scoliosis, and short stature, are common in affected individuals. Molecular defects in this pathway may impact bone homeostasis and create potential targets for pharmaceutical intervention.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Pediatrics
B. Ciacchini, G. Di Nardo, M. Marin, E. Borali, M. Caraccia, R. Mogni, F. Cairello, I. Rabbone, G. B. Ferrero, A. Pini Prato, E. Felici
Summary: This report describes a case of cardio-facio-cutaneous syndrome, a rare genetic disorder, characterized by craniofacial, dermatologic and cardiac defects. The patient experienced severe feeding difficulties, which led to growth arrest and malnutrition. Treatment including nasogastric tube placement and laparoscopic surgeries improved the patient's condition.
FRONTIERS IN PEDIATRICS
(2023)
Article
Genetics & Heredity
Victorya Zakharova, Elena Raykina, Irina Mersiyanova, Ekaterina Deordieva, Dmitry Pershin, Victorya Vedmedskia, Yulia Rodina, Natalia Kuzmenko, Michael Maschan, Anna Shcherbina
Summary: RASopathies are disorders caused by germline mutations in genes that encode components of the RAS/MAPK pathway. These disorders are characterized by developmental delay, facial dysmorphisms, organ defects, and increased cancer susceptibility. This study reports a case of RASopathy caused by a cancer-associated MAP2K1 mutation, which is of postzygotic mosaic nature and may explain the patient's survival.
Article
Genetics & Heredity
Emanuele Crincoli, Chiara Leoni, Germana Viscogliosi, Roberta Onesimo, Roberta Mattei, Marco Tartaglia, Fiammetta Catania, Stanislao Rizzo, Giuseppe Zampino, Annabella Salerni
Summary: Cardio-facio-cutaneous syndrome (CFCS) is a rare genetic disorder caused by upregulated RAS/MAPK signaling. This study investigates the prevalence of ophthalmologic abnormalities in CFCS patients and explores genotype-endophenotype correlations. The findings suggest that CFCS patients with BRAF mutations have a higher risk of visual impairment and refractive errors, while patients with mutations in other genes have a higher prevalence of myopia. Pale optic disc is associated with specific eye muscle abnormalities. Early ophthalmologic referral is recommended for CFCS patients, especially those with BRAF mutations, due to the high risk of amblyopia.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Chiara Leoni, Domenico Marco Romeo, Michele Pelliccioni, Mariangela Di Gia, Roberta Onesimo, Valentina Giorgio, Elisabetta Flex, Marta Tedesco, Marco Tartaglia, Donato Rigante, Antonio Valassina, Giuseppe Zampino
Summary: Orthopedic manifestations are common in patients with Costello syndrome and cardio-facio-cutaneous syndrome, with differences in severity and characteristics based on genetic variants. Functional assessments by using 6MWT and PODCI could help evaluate the impact on patient outcomes and guide tailored treatment approaches.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Genetics & Heredity
Chiara Leoni, Germana Viscogliosi, Roberta Onesimo, Cristian Bisanti, Miriam Massese, Valentina Giorgio, Fabio Corbo, Marta Tedesco, Anna Acampora, Clelia Cipolla, Claudia Dell'Atti, Elisabetta Flex, Jacopo Gervasoni, Aniello Primiano, Donato Rigante, Marco Tartaglia, Giuseppe Zampino
Summary: CFCS is characterized by decreased bone mineral density, with BMD z-scores and t-scores below the reference range. Monitoring bone health is crucial for affected individuals.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Genetics & Heredity
Tadashi Shiohama, Katsunori Fujii, Rika Kosaki, Yoshimi Watanabe, Tomoko Uchida, Sho Hagiwara, Kaori Kinoshita, Katsuo Sugita, Yoko Aoki, Naoki Shimojo
Summary: Cardio-facio-cutaneous syndrome (CFC) is a congenital disease associated with constitutive activation of the Raf/MEK/ERK signaling cascade. This study reports severe neuroglycopenic symptoms in two children with CFC and identifies brain lesions through magnetic resonance imaging.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Review
Genetics & Heredity
Xiaoao Dong, Nicholas C. Y. Png, Marielle V. Fortier, Jiin Ying Lim, Kenneth P. L. Wong, Jonathan T. L. Choo, Ene Choo Tan, Saumya Shekhar Jamuar
Summary: CFC syndrome is a rare genetic condition caused mainly by mutations in the BRAF gene and rarely by mutations in the KRAS gene. It is characterized by cardiac abnormalities, craniofacial dysmorphism, and cutaneous abnormalities. This study reports a case of symmetrical polyostotic fibrous dysplasia (FD) in a patient with CFC syndrome, suggesting a possible new clinical feature.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Genetics & Heredity
Angie C. Jelin, Amanda Mahle, Susan H. Tran, Teresa N. Sparks, Katherine A. Rauen
Summary: The study systematically describes the prenatal phenotype, obstetrical and neonatal outcomes of the RASopathy CFC syndrome. By analyzing the medical history data of children with CFC, it is found that there are various maternal characteristics, pregnancy complications, and prenatal and birth abnormalities. These findings contribute to better prenatal prognostic counseling and outcomes.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Pediatrics
Gregorio Serra, Sofia Felice, Vincenzo Antona, Maria Rita Di Pace, Mario Giuffre, Ettore Piro, Giovanni Corsello
Summary: Cardio-facio-cutaneous syndrome (CFCS) is a rare syndrome caused by mutations in genes of the RAS/MAPK pathway. It is characterized by facial dysmorphisms, growth failure, heart defects, developmental delay, and ectodermal abnormalities. The 19p13.3 microdeletion, including the MAP 2 K2 gene, has been associated with a more severe phenotype in CFCS patients.
ITALIAN JOURNAL OF PEDIATRICS
(2022)
Article
Oncology
Georgia Kontogianni, Konstantinos Voutetakis, Georgia Piroti, Katerina Kypreou, Irene Stefanaki, Efstathios Iason Vlachavas, Eleftherios Pilalis, Alexander Stratigos, Aristotelis Chatziioannou, Olga Papadodima
Summary: This study aimed to characterize patients with primary cutaneous melanoma (CM) by analyzing both germline and somatic variations as well as alterations at the gene expression level. Oncogenic alterations were identified and phenotypic cell states were inferred from transcriptomic data. Integrating mutational and transcriptomic data could provide insights into genes and pathways involved in the maintenance of phenotypic states in primary melanomas.
Article
Anatomy & Morphology
Yoshiko Maeda, William E. Tidyman, Bradley P. Ander, Catrin A. Pritchard, Katherine A. Rauen
Summary: Cardio-facio-cutaneous (CFC) syndrome is a congenital anomaly syndrome caused by activating mutations in BRAF, MEK1, or MEK2 kinases. A mouse model with an activating Braf(L597V) allele was used to study skeletal muscle myopathy in CFC, revealing phenotypic alterations and global transcriptional dysregulation. Inhibition of myofiber differentiation can be rescued by MEK inhibition, suggesting therapeutic potential for RASopathy patients.
DEVELOPMENTAL DYNAMICS
(2021)
Article
Pediatrics
Aleksandra Szczawinska-Poplonyk, Natalia Poplonyk, Marek Niedziela, Anna Sowinska-Seidler, Pawel Sztromwasser, Aleksander Jamsheer, Monika Obara-Moszynska
Summary: Cardio-facio-cutaneous syndrome (CFCS) is a clinical disorder characterized by disruptions in the RAS/MAPK signaling pathway. This study reports a patient with CFCS who also showed immunodeficiency and growth hormone deficiency. Using whole genome sequencing, a novel pathogenic variant in the MAP2K1 gene was identified. Replacement immunoglobulin therapy and timely antibiotic prophylaxis were effective in the treatment of this patient.
FRONTIERS IN PEDIATRICS
(2022)
Article
Obstetrics & Gynecology
Songchang Chen, Xuyang Yin, Sijia Zhang, Jun Xia, Ping Liu, Pingyuan Xie, Huijuan Yan, Xinming Liang, Junyu Zhang, Yiyao Chen, Hongjun Fei, Lanlan Zhang, Yuting Hu, Hui Jiang, Ge Lin, Fang Chen, Chenming Xu
Summary: WGS offers a cost-effective and reliable approach for genome-wide haplotyping and PGT for monogenic disorders, aneuploidy, and structural rearrangements without the need for additional family members, showing 100% concordance with traditional PGT methods.
HUMAN REPRODUCTION
(2021)
Article
Genetics & Heredity
Rafael Hencke Tresbach, Fernanda Sperb-Ludwig, Rodrigo Ligabue-Braun, Tassia Tonon, Maria Teresinha de Oliveira Cardoso, Romina Soledad Heredia, Maria Teresa Alves da Silva Rosa, Barbara Catia Martins, Monique Oliveira Poubel, Luiz Carlos Santana da Silva, Francois Maillot, Ida Vanessa Doederlein Schwartz
Summary: Thirty-four Brazilian patients with PKU were analyzed using next-generation sequencing, revealing 26 different pathogenic variants. A novel pathogenic variant was found that may affect the stability and activity of the PAH enzyme.
Article
Oncology
Carla Escudeiro, Carla Pinto, Joana Vieira, Ana Peixoto, Pedro Pinto, Manuela Pinheiro, Catarina Santos, Joana Guerra, Susana Lisboa, Rui Santos, Joao Silva, Conceicao Leal, Nuno Coimbra, Paula Lopes, Marco Ferreira, Ana B. Sousa, Manuel R. Teixeira
Summary: Breast cancer is a frequent event in Li-Fraumeni syndrome associated with germline TP53 variants, particularly in HER2-positive cases. This study evaluated the prevalence of TP53 germline variants in young women with HER2-positive breast cancer and found a small proportion of cases with deleterious TP53 variants, which showed higher levels of HER2 amplification compared to non-carriers. All TP53 pathogenic variant carriers in this study had their first breast carcinoma diagnosed at age 31 or younger and a first-degree relative with early-onset cancer. Further research is needed to determine the utility of HER2 status in early-onset breast cancer patients for updating TP53 testing criteria.
Article
Gastroenterology & Hepatology
Olga P. Nyssen, Dmitry Bordin, Bojan Tepes, Angeles Perez-Aisa, Dino Vaira, Maria Caldas, Luis Bujanda, Manuel Castro-Fernandez, Frode Lerang, Marcis Leja, Luis Rodrigo, Theodore Rokkas, Limas Kupcinskas, Jorge Perez-Lasala, Laimas Jonaitis, Oleg Shvets, Antonio Gasbarrini, Halis Simsek, Anthony T. R. Axon, Gyorgy Buzas, Jose Carlos Machado, Yaron Niv, Lyudmila Boyanova, Adrian Goldis, Vincent Lamy, Ante Tonkic, Krzysztof Przytulski, Christoph Beglinger, Marino Venerito, Peter Bytzer, Lisette Capelle, Tomica Milosavljevic, Vladimir Milivojevic, Lea Veijola, Javier Molina-Infante, Liudmila Vologzhanina, Galina Fadeenko, Ines Arino, Giulia Fiorini, Ana Garre, Jesus Garrido, Cristina F. Perez, Ignasi Puig, Frederic Heluwaert, Francis Megraud, Colm O'Morain, Javier P. Gisbert
Summary: The study aimed to evaluate the decision-making and outcomes in Helicobacter pylori management by European gastroenterologists, finding that management of H. pylori infection is heterogeneous, with only quadruple therapies able to achieve over 90% eradication rates, and European recommendations are slowly and heterogeneously being incorporated into routine clinical practice.
Review
Oncology
Marina Morais, Diogo Melo Pinto, Jose Carlos Machado, Silvestre Carneiro
Summary: Liquid biopsy, as a non-invasive detection method, holds potential value in predicting treatment response and prognosis for LARC patients. However, the application of liquid biopsy in this field remains controversial and inconclusive, requiring further research to determine the optimal methods and timing.
Article
Gastroenterology & Hepatology
Carolina F. Ruivo, Nuno Bastos, Barbara Adem, Ines Batista, Cecilia Duraes, Carlos A. Melo, Stephanie A. Castaldo, Francisco Campos-Laborie, Pedro Moutinho-Ribeiro, Barbara Morao, Ana Costa-Pinto, Soraia Silva, Hugo Osorio, Sergio Ciordia, Jose Luis Costa, David Goodrich, Bruno Cavadas, Luisa Pereira, Tony Kouzarides, Guilherme Macedo, Rui Maio, Fatima Carneiro, Marilia Cravo, Raghu Kalluri, Jose Carlos Machado, Sonia A. Melo
Summary: This study reveals that pancreatic ductal adenocarcinoma (PDAC) tumors establish a communication network mediated by cancer stem cells (CSC) and the protein agrin, which promotes tumor growth and therapy resistance. CSC release extracellular vesicles (EVs) that activate specific proteins, leading to increased tumor cell proliferation and transcriptional regulator activation. Targeting this communication network may provide a potential strategy for targeted therapy and has significant implications for cancer stem cells.
Article
Health Care Sciences & Services
Francisco Silva, Tania Pereira, Ines Neves, Joana Morgado, Claudia Freitas, Mafalda Malafaia, Joana Sousa, Joao Fonseca, Eduardo Negrao, Beatriz Flor de Lima, Miguel Correia da Silva, Antonio J. Madureira, Isabel Ramos, Jose Luis Costa, Venceslau Hespanhol, Antonio Cunha, Helder P. Oliveira
Summary: Advancements in computer-aided decision systems have brought significant benefits to healthcare, particularly in the field of lung cancer where accurate clinical procedures are crucial. This review focuses on the development of CAD tools using computed tomography images for lung cancer-related tasks and discusses current challenges and future directions in integrating artificial intelligence in healthcare.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Cardiac & Cardiovascular Systems
Arsonval Lamounier Junior, Alba Guitian Gonzalez, Alejandro Rodriguez Vilela, Alfredo Reparaz Andrade, Alvaro Rubio Alcaide, Ana Berta Sousa, Carmen Benito Lopez, Diego Alonso Garcia, German Fernandez Ferro, Ines Cruz, Ivonne Johana Cardenas Reyes, Joel Salazar-Mendiguchia Garcia, Jose Maria Larranaga-Moreira, Juan Pablo Ochoa, Julian Palomino-Doza, Luis de la Higuera Romero, Marcos Nicolas Cicerchia, Maria Alejandra Restrepo Cordoba, Maria Luisa Pena-Pena, Maria Noel Brogger, Marilia Loureiro, Maria Victoria Mogollon Jimenez, Raquel Bilbao Quesada, Raul Franco Gutierrez, Soledad Garcia Hernandez, Tomas Ripoll-Vera, Xusto Fernandez, Olga Azevedo, Pablo Garcia Pavia, Luis R. Lopes, Martin Ortiz, Dulce Brito, Roberto Barriales-Villa, Lorenzo Monserrat Iglesias
Summary: TPM1 p.Arg21Leu is a pathogenic variant of HCM associated with late-onset/incomplete penetrance and a generally favorable prognosis. The variant was found in 0.61% of HCM cases and showed significant cosegregation in families. Survival rate and HCM sudden death risk were within acceptable ranges.
REVISTA ESPANOLA DE CARDIOLOGIA
(2022)
Article
Medicine, General & Internal
Manuel R. Teixeira, Julio Oliveira, Paula Borralho, Maria Gabriela O. Fernandes, Teresa Almodovar, Isabel Fernandes, Daniela Macedo, Ana Ferreira, Ana Barroso, Encarnacao Teixeira, Jose Carlos Machado
Summary: Next-generation sequencing (NGS) is widely used in clinical oncology for diagnosis, prognosis, and therapeutic guidance. In the context of lung cancer and rare tumors, it is important to address multiple quality control checkpoints and improve communication between clinicians and laboratory support. NGS panels are recommended for comprehensive genomic profiling in rare tumors. Multidisciplinary tumor boards are essential for tailoring the best strategy for each patient.
ACTA MEDICA PORTUGUESA
(2022)
Article
Gastroenterology & Hepatology
Peter Malfertheiner, Francis Megraud, Theodore Rokkas, Javier P. Gisbert, Jyh-Ming Liou, Christian Schulz, Antonio Gasbarrini, Richard H. Hunt, Marcis Leja, Colm O'Morain, Massimo Rugge, Sebastian Suerbaum, Herbert Tilg, Kentaro Sugano, Emad M. El-Omar
Summary: Helicobacter pylori infection is recognized as an infectious disease and requires optimized management to prevent complications and gastric cancer. Continuous updates in treatment strategies and testing methods are necessary due to rising antibiotic resistance and the impact on gut microbiota.
Article
Genetics & Heredity
Cristina Santos, Andreia Almeida, Rita Pinto, Karolina Kaminska, Virginie G. Peter, Ana-Berta Sousa, Carlo Rivolta, Luisa Coutinho-Santos
OPHTHALMIC GENETICS
(2022)
Letter
Respiratory System
M. Costa e Silva, I. Sucena, L. Cirnes, J. C. Machado, S. Campainha, A. Barroso
Article
Chemistry, Medicinal
Marina Morais, Telma Fonseca, Diogo Melo-Pinto, Isabel Prieto, Ana Teresa Vilares, Ana Luisa Duarte, Patricia Leitao, Luis Cirnes, Jose Carlos Machado, Silvestre Carneiro
Summary: Watch and wait is being used as a treatment option for locally advanced rectal cancer patients. However, there is no accurate clinical modality for predicting the response to treatment. This study suggests that ctDNA combined with mrEMVI may help predict the response and disease-free survival in these patients.
Article
Medicine, General & Internal
Joana Espiga De Macedo, Tiago Taveira-Gomes, Jose Carlos Machado, Venceslau Hespanhol
Summary: This study aimed to assess the impact of ctDNA analysis in early-stage lung cancer. The results showed that the maximum yield of ctDNA was obtained at the surgical discharge, and the pre-operatory time point offered the highest sensitivity for the detection of actionable mutations in early-stage lung cancer.
ACTA MEDICA PORTUGUESA
(2023)
Article
Biochemistry & Molecular Biology
Nicola Normanno, Jose Carlos Machado, Edoardo Pescarmona, Simonetta Buglioni, Lara Navarro, Riziero Esposito Abate, Anabela Ferro, Rob Mensink, Matilde Lambiase, Virginie Lespinet-Fabre, Byron Calgua, Philip M. Jermann, Marius Ilie, Paul Hofman
Summary: This multicenter study evaluated the performance of the Oncomine Dx Express Test on the Ion Torrent Genexus System for detecting DNA and RNA variants in solid tumors. The test showed high accuracy and sensitivity, providing results in a short turnaround time, which can support timely decision-making for targeted therapeutic interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Manuel R. Teixeira, Julio Oliveira, Paula Borralho, Maria Gabriela O. Fernandes, Teresa Almodovar, Isabel Fernandes, Daniela Macedo, Ana Ferreira, Ana Barroso, Encarnacao Teixeira, Jose Carlos Machado
Summary: This article highlights the importance of using Next-generation sequencing (NGS) in clinical oncology for diagnosis, prognosis, and therapeutic guidance. It focuses on the application of NGS in lung cancer, rare cancers, and cancers of unknown primary, emphasizing the need for quality control and communication between clinicians and laboratories. The article also underscores the significance of multidisciplinary tumor boards in tailoring the best strategy for each patient.
ACTA MEDICA PORTUGUESA
(2022)
Meeting Abstract
Oncology
Jorge Lima, Jorge Pinheiro, Susana Nunes, Ana Paula Fernandes, Paula Soares, Jose Carlos Machado, Josue Pereira, Maria Joao Gil da Costa