Article
Clinical Neurology
Cathal John Hannan, Charlotte Hammerbeck-Ward, Omar Nathan Pathmanaban, Miriam J. Smith, Scott A. A. Rutherford, Simon K. K. Lloyd, Simon Richard Mackenzie Freeman, Andrew J. Wallace, Andrew Thomas King, Dafydd Gareth Richard Evans
Summary: Patients presenting with unilateral vestibular schwannomas (UVS) and multiple meningiomas (MM) are more likely to be diagnosed with neurofibromatosis type 2 (NF2) compared to patients with UVS and multiple nonintradermal schwannomas (NIDS), but less likely to develop bilateral vestibular schwannomas. Some patients with MM without meeting NF2 criteria have pathogenic variants in SMARCE1 and mosaic NF2.
Review
Biochemistry & Molecular Biology
Ryota Tamura
Summary: Neurofibromatosis is a neurocutaneous syndrome characterized by tumors in the nervous system, with NF1, NF2, and SWN as its three main types. While NF1 and NF2 have known genetic mutations and targeted therapies, the molecular mechanisms of SWN remain unclear and require further research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Nida Fatima, Anna La Dine, Zachary R. Barnard, Gregory P. Lekovic
Summary: Segmental neurofibromatosis (SNF) is a rare subtype of neurofibromatosis (NF) characterized by localized skin and/or subcutaneous manifestations. Spinal neurofibromatosis, on the other hand, is characterized by histologically proven bilateral neurofibromas of the spinal roots. This case report describes a novel manifestation of spinal SNF and discusses treatment options for this rare phenotype.
NEUROLOGICAL SCIENCES
(2022)
Article
Genetics & Heredity
Scott R. Plotkin, Ludwine Messiaen, Eric Legius, Patrice Pancza, Robert A. Avery, Jaishri O. Blakeley, Dusica Babovic-Vuksanovic, Rosalie Ferner, Michael J. Fisher, Jan M. Friedman, Marco Giovannini, David H. Gutmann, Clemens Oliver Hanemann, Michel Kalamarides, Hildegard Kehrer-Sawatzki, Bruce R. Korf, Victor-Felix Mautner, Mia MacCollin, Laura Papi, Katherine A. Rauen, Vincent Riccardi, Elizabeth Schorry, Miriam J. Smith, Anat Stemmer-Rachamimov, David A. Stevenson, Nicole J. Ullrich, David Viskochil, Katharina Wimmer, Kaleb Yohay, Susan M. Huson, Pierre Wolkenstein, D. Gareth Evans
Summary: The study aims to update the diagnostic criteria for neurofibromatosis type 2 (NF2) and schwannomatosis (SWN) by incorporating recent advances in genetics, ophthalmology, neuropathology, and neuroimaging. The updated criteria include clinical features and genetic testing, emphasizing the phenotypic overlap between the two conditions.
GENETICS IN MEDICINE
(2022)
Editorial Material
Radiology, Nuclear Medicine & Medical Imaging
Nuh Filizoglu, Salih Ozguven
Summary: Neurofibromatosis type 2 (NF2) is an autosomal-dominant tumor predisposing syndrome characterized by bilateral vestibular schwannomas. However, other nervous system tumors can also be seen in patients with NF2.
CLINICAL NUCLEAR MEDICINE
(2022)
Article
Oncology
Isabel Gugel, Florian Grimm, Marcos Tatagiba, Martin U. Schuhmann, Julian Zipfel
Summary: Resection of peripheral and intraspinal schwannomas is an effective and low-risk treatment in both NF2 and SWNT. Patients with severe pain have a particular benefit from surgical treatment. Intraspinal lesions are associated with worse neurological function whereas peripheral lesions showed a higher pain intensity.
JOURNAL OF NEURO-ONCOLOGY
(2022)
Article
Clinical Neurology
Phanidhar Kukutla, Sherif G. Ahmed, Daniel M. DuBreuil, Ahmed Abdelnabi, Murat Cetinbas, Giulia Fulci, Berent Aldikacti, Anat Stemmer-Rachamimov, Scott R. Plotkin, Brian Wainger, Ruslan I. Sadreyev, Gary J. Brenner
Summary: Schwannomas can cause severe pain, and the upregulation of FGF7 in painful tumors may be associated with the development of pain. Behavioral support was found in a xenograft human NF2-schwannoma model, where over-expression of FGF7 induced pain behavior in nude mice.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Dermatology
A. Plana-Pla, B. Garcia, M. Munera-Campos, N. Catasus, E. Serra Arenas, I Blanco, E. Castellanos Perez, I Bielsa
Summary: This study characterized cutaneous lesions in a Spanish cohort of patients with NF2 and investigated associations with clinical and genetic severity. The findings showed that cutaneous lesions, especially plexiform schwannomas, are common in NF2 and usually appear at an early age, providing useful diagnostic and prognostic information.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2022)
Article
Genetics & Heredity
Rebecca Burns, Kristin Niendorf, Kathleen Steinberg, Amy Mueller, Ina Ly, Justin T. Jordan, Scott R. Plotkin, Stephanie R. Hicks
Summary: This study compared the efficacy of germline-only versus paired genetic testing in clarifying the diagnosis of patients with features of NF2 and SWN. The results showed that paired testing had a higher likelihood of providing diagnostic clarity, especially for patients who had analysis of multiple tumors.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Clinical Neurology
Jianwei Shi, Dafeng Lu, Ruxin Gu, Jing Xie, Li Yu, Xin Sun, Yansong Zhang
Summary: This study conducted a comprehensive bioinformatic analysis of methylated-differentially expressed genes (MDEGs) in NF2-VS, identifying genes and pathways associated with the condition. Potential pharmacotherapy targeting MDEGs was extracted for NF2-VS, providing valuable insights into the molecular mechanisms and potential therapeutic targets for NF2-VS.
WORLD NEUROSURGERY
(2022)
Article
Orthopedics
Hooman Shariatzadeh, Shayan Amiri, Samad Joudi, Mehrdad Bahrabadi
Summary: This study reports a case of a 45-year-old man with multiple schwannomas without manifestations of neurofibromatosis. Surgery revealed four tumors in the sciatic nerve, characteristic of schwannoma. The case highlights the rare occurrence of multiple schwannomas without neurofibromatosis.
ARCHIVES OF BONE AND JOINT SURGERY-ABJS
(2021)
Review
Oncology
Evan C. Cumpston, Steven D. Rhodes, Charles W. Yates
Summary: Neurofibromatosis 2 (NF2) is a genetic disorder characterized by various tumors. Recent studies have provided new insights into the role of NF2 gene and merlin in the development of vestibular schwannomas (VS).
CURRENT ONCOLOGY REPORTS
(2023)
Article
Oncology
Jules P. J. Douwes, Kimberley S. Koetsier, Victor S. van Dam, Scott R. Plotkin, Frederick G. Barker, D. Bradley Welling, Jeroen C. Jansen, Erik F. Hensen, Helen A. Shih
Summary: The management of vestibular schwannomas in neurofibromatosis type 2-related schwannomatosis (NF2) is complex. Current treatment strategies include active surveillance, surgery, radiotherapy, and pharmacotherapy. This study found that the majority of NF2 patients was treated with proton radiotherapy as salvage treatment for vestibular schwannoma. However, they did experience significant tumor and/or treatment-related side effects. The value of proton radiotherapy as a primary treatment for vestibular schwannomas in NF2 patients remains to be determined.
Article
Genetics & Heredity
Arkadiusz Piotrowski, Magdalena Koczkowska, Andrzej B. Poplawski, Rafal Bartoszewski, Jaroslaw Kroliczewski, Alina Mieczkowska, Alicia Gomes, Michael R. Crowley, David K. Crossman, Yunjia Chen, Ping Lao, Eduard Serra, Meritxell C. Llach, Elisabeth Castellanos, Ludwine M. Messiaen
Summary: Constitutional pathogenic variants in genes LZTR1 or SMARCB1 were identified in a high percentage of familial and sporadic schwannomatosis cases, with additional novel variants and potential predisposing candidate genes revealed through extensive sequencing.
Article
Genetics & Heredity
Jineta Banerjee, Jan M. Friedman, Laura J. Klesse, Kaleb H. Yohay, Justin T. Jordan, Scott R. Plotkin, Robert J. Allaway, Jaishri O. Blakeley
Summary: This study investigated whether patients with rare diseases such as neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), or schwannomatosis (SWN) are more susceptible to SARS-CoV-2 infection and severe COVID-19. The results showed that the proportion of positive cases in NF1, NF2, or SWN patients was not significantly higher than in individuals without these rare diseases. There were no severe outcomes reported in the NF2 or SWN cohorts, and the proportion of severe outcomes in NF1 patients was similar to other rare disease cohorts and the general population.
GENETICS IN MEDICINE
(2023)
Article
Dermatology
Adria Plana-Pla, Laura Condal, Ane Jaka, Ignacio Blanco, Elisabeth Castellanos, Isabel Bielsa
Summary: Linear Cowden nevus is an epidermal nevus that mainly occurs in patients with PTEN hamartoma tumor syndrome and has certain clinical features distinguishing it from similar conditions.
PEDIATRIC DERMATOLOGY
(2023)
Article
Infectious Diseases
Clara Suner, Maria Ubals, Eloy Jose Tarin-Vicente, Adria Mendoza, Andrea Alemany, Agueda Hernandez-Rodriguez, Cristina Casan, Vicente Descalzo, Dan Ouchi, Aurelien Marc, Angel Rivero, Pep Coll, Xenia Oller, Jose Miguel Cabrera, Marti Vall-Mayans, Marfa Dolores Folgueira, Marfa angeles Melendez, Manuel Agud-Dios, Elena Gil-Cruz, Alexia Paris de Leon, Afda Ramfrez Marinero, Vira Buhiichyk, Cristina Galvan-Casas, Roger Paredes, Nuria Prat, Maria-Rosa Sala Farre, Josep Maria Bonet-Simo, Magf Farre, Pablo L. Ortiz-Romero, Bonaventura Clotet, Vicente Garcia-Patos, Jordi Casabona, Jeremie Guedj, Pere-Joan Cardona, Ignacio Blanco, Michael Marks, Oriol Mitja
Summary: This study aimed to characterize the viral load kinetics over time in various parts of the body in patients with monkeypox. The results showed that the clearance time of the virus varied in different body locations. Semen testing and prolonged use of condoms might not be necessary after recovery from monkeypox.
LANCET INFECTIOUS DISEASES
(2023)
Article
Oncology
Jose Garcia-Pelaez, Rita Barbosa-Matos, Silvana Lobo, Alexandre Dias, Luzia Garrido, Sergio Castedo, Sonia Sousa, Hugo Pinheiro, Liliana Sousa, Rita Monteiro, Joaquin J. Maqueda, Susana Fernandes, Fatima Carneiro, Nadia Pinto, Carolina Lemos, Carla Pinto, Manuel R. Teixeira, Stefan Aretz, Svetlana Bajalica-Lagercrantz, Judith Balmana, Ana Blatnik, Patrick R. Benusiglio, Maud Blanluet, Vincent Bours, Hilde Brems, Joan Brunet, Daniele Calistri, Gabriel Capella, Sergio Carrera, Chrystelle Colas, Karin Dahan, Robin de Putter, Camille Desseignes, Elena Dominguez-Garrido, Conceicao Egas, D. Gareth Evans, Damien Feret, Eleanor Fewings, Rebecca C. Fitzgerald, Florence Coulet, Maria Garcia-Barcina, Maurizio Genuardi, Lisa Golmard, Karl Hackmann, Helen Hanson, Elke Holinski-Feder, Robert Huneburg, Mateja Krajc, Kristina Lagerstedt-Robinson, Conxi Lazaro, Marjolijn J. L. Ligtenberg, Cristina Martinez-Bouzas, Sonia Merino, Genevieve Michils, Srdjan Novakovic, Ana Patino-Garcia, Guglielmina Nadia Ranzani, Evelin Schrock, Ines Silva, Catarina Silveira, Jose L. Soto, Isabel Spier, Verena Steinke-Lange, Gianluca Tedaldi, Maria-Isabel Tejada, Emma R. Woodward, Marc Tischkowitz, Nicoline Hoogerbrugge, Carla Oliveira
Summary: This study analyzed families carrying rare CDH1 variants, comparing the cancer spectrum in carriers of pathogenic or likely pathogenic variants (PV/LPV) or missense variants of unknown significance, and evaluated the performance of expanded criteria for CDH1 testing. The results showed that PV/LPV carriers were positively associated with lobular breast cancer, diffuse gastric cancer, and gastric cancer, while missense variants of unknown significance did not show this positive association.
Article
Multidisciplinary Sciences
Miriam Magallon-Lorenz, Ernest Terribas, Sara Ortega-Bertran, Edgar Creus-Bachiller, Marco Fernandez, Gerard Requena, Inma Rosas, Helena Mazuelas, Itziar Uriarte-Arrazola, Alex Negro, Tereza Lausova, Elisabeth Castellanos, Ignacio Blanco, George DeVries, Hiroyuki Kawashima, Eric Legius, Hilde Brems, Viktor Mautner, Lan Kluwe, Nancy Ratner, Margaret Wallace, Juana Fernandez-Rodriguez, Conxi Lazaro, Jonathan A. Fletcher, David Reuss, Meritxell Carrio, Bernat Gel, Eduard Serra
Summary: This article presents the genomic characterization of 9 widely used human MPNST cell lines, providing valuable resources for translational research. NF1-related cell lines exhibited characteristics similar to primary MPNSTs, while sporadic cell lines showed different inactivation patterns of tumor suppressor genes and mutations. The re-classification of cell lines as melanomas and other sarcomas demonstrated different responses to drug treatment. Deep genomic analysis, methylome-based classification, and cell-identity marker expression challenged the identity of common MPNST cell lines, highlighting the need for revisions in MPNST diagnosis.
Review
Medicine, General & Internal
Charlotte Carton, D. Gareth Evans, Ignacio Blanco, Reinhard E. Friedrich, Rosalie E. Ferner, Said Farschtschi, Hector Salvador, Amedeo A. Azizi, Victor Mautner, Claas Roehl, Sirkku Peltonen, Stavros Stivaros, Eric Legius, Rianne Oostenbrink
Summary: This study aims to integrate information on NF1-associated tumors to assist healthcare professionals in tumor surveillance of NF1 individuals. Personalized and targeted tumor management proposals have been defined to ensure appropriate care for those in need.
Article
Toxicology
Alberto F. Maroto, Mireia Borrajo, Silvia Prades, Angela Callejo, Emilio Amilibia, Marta Perez-Grau, Francesc Roca-Ribas, Elisabeth Castellanos, Alejandro Barrallo-Gimeno, Jordi Llorens
Summary: Hair cell (HC) loss by epithelial extrusion is preceded by the dismantlement of the calyceal junction in the contact between type I HC (HCI) and calyx afferent terminals, suggesting a common response triggered by chronic stress before HCI loss. This phenomenon was observed in both rat models treated with streptomycin and human samples obtained during therapeutic procedures. The reversible dismantlement of the vestibular calyceal junction may partly explain the recovery of function loss after aminoglycoside exposure.
ARCHIVES OF TOXICOLOGY
(2023)
Article
Biochemical Research Methods
Elisabet Munte, Lidia Feliubadalo, Marta Pineda, Eva Tornero, Maribel Gonzalez, Jose Marcos Moreno-Cabrera, Carla Roca, Joan Bales Rubio, Laura Arnaldo, Gabriel Capella, Jose Luis Mosquera, Conxi Lazaro
Summary: The study developed a software package called vaRHC to assist in variant classification in hereditary cancer. The package collects information from diverse databases and assigns or denies different types of evidence based on the latest international guidelines for specific genes or general criteria for other genes. It provides an automated variant classification using a Bayesian metastructure and considers CanVIG-UK recommendations, showing a better criteria assignment than a similar tool called Cancer SIGVAR. The source code of the package can be accessed on the GitHub repository and will be submitted to CRAN soon.
Article
Genetics & Heredity
Adria Lopez-Fernandez, Guillermo Villacampa, Monica Salinas, Elia Grau, Esther Darder, Estela Carrasco, Ares Solanes, Angela Velasco, Maite Torres, Elisabet Munte, Silvia Iglesias, Sara Torres-Esquius, Noemi Tuset, Orland Diez, Conxi Lazaro, Joan Brunet, Sergi Corbella, Judith Balmana
Summary: This study aims to analyze the psychological impact of genetic testing and to identify the profile of individuals at higher risk. Factors such as high neuroticism score, high baseline cancer worry, and a positive genetic test result were found to be independently associated with higher psychological impact. The highest risk profile consisted of women with high levels of neuroticism and a positive result. Uncertainty was mainly associated with high neuroticism levels, regardless of the genetic test result. A holistic approach to personalized genetic counseling should include the assessment of personality dimensions.
JOURNAL OF GENETIC COUNSELING
(2023)
Article
Dermatology
Verena Staedtke, Piotr Topilko, Lu Q. Le, Kevin Grimes, David A. Largaespada, Ross L. Cagan, Matthew R. Steensma, Anat Stemmer-Rachamimov, Jaishri O. Blakeley, Steven D. Rhodes, Ina Ly, Carlos G. Romo, Sang Y. Lee, Eduard Serra
Summary: Neurofibromatosis type 1 (NF1) is caused by a nonfunctional NF1 tumor suppressor gene, resulting in the development of cutaneous neurofibromas (cNFs). Incomplete understanding of cNF pathophysiology and limitations in experimental modeling have hindered the development of cNF treatment. Recent advances in preclinical in vitro and in vivo modeling provide unprecedented opportunities for therapeutic discovery and improving our understanding of cNF biology.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Dermatology
Chunhui Jiang, Renee M. Mckay, Sang Y. Lee, Carlos G. Romo, Jaishri O. Blakeley, Muzlifah Haniffa, Eduard Serra, Matthew R. Steensma, David Largaespada, Lu Q. Le
Summary: Neurofibromatosis type 1 is a common genetic disorder that predisposes patients to develop tumors. Cutaneous neurofibromas significantly impact patients' quality of life due to their unaesthetic appearance and physical discomfort. Understanding the factors involved in the heterogeneity of cNF can help develop personalized treatment regimens.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Dermatology
Jaishri O. Blakeley, Lu Q. Le, Sang Y. Lee, Ina Ly, Steven D. Rhodes, Carlos G. Romo, Kavita Y. Sarin, Verena Staedtke, Matthew R. Steensma, Pierre Wolkenstein
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Biochemical Research Methods
Helena Mazuelas, Itziar Uriarte-Arrazola, Juana Fernandez-Rodriguez, Miriam Magallon-Lorenz, Alberto Villanueva, Conxi Lazaro, Bernat Gel, Eduard Serra, Meritxell Carrio
Summary: This study generated neurofibromaspheres by differentiating NF1(-/-) Schwann cells from induced pluripotent stem cells and combining them with neurofibroma primary fibroblasts. Neurofibroma-like tumors were developed when these neurofibromaspheres were engrafted in the sciatic nerve of nude mice. This model provides a versatile platform for drug screening and the study of neurofibroma biology.
Article
Oncology
Edgar Creus-Bachiller, Juana Fernandez-Rodriguez, Miriam Magallon-Lorenz, Sara Ortega-Bertran, Susana Navas-Rutete, Cleofe Romagosa, Tulio M. Silva, Maria Pane, Anna Estival, Diana Perez Sidelnikova, Mireia Morell, Helena Mazuelas, Meritxell Carrio, Tereza Lausova, David Reuss, Bernat Gel, Alberto Villanueva, Eduard Serra, Conxi Lazaro
Summary: This study presents an extension of an MPNST precision medicine platform, incorporating new PDOXs and cell lines that accurately recapitulate the characteristics of primary tumors. The diverse tumor identities and associated genomic alterations impact treatment responses, highlighting the importance of correct preclinical information for guiding MPNST clinical trials.
MOLECULAR ONCOLOGY
(2023)