Article
Clinical Neurology
V Montano, D. Orsucci, V Carelli, C. La Morgia, M. L. Valentino, C. Lamperti, S. Marchet, O. Musumeci, A. Toscano, G. Primiano, F. M. Santorelli, C. Ticci, M. Filosto, A. Rubegni, T. Mongini, P. Tonin, S. Servidei, R. Ceravolo, G. Siciliano, Michelangelo Mancuso
Summary: The study reviewed the prevalence and clinical features of movement disorders in adults with primary mitochondrial diseases of the Italian Collaborative Network of Mitochondrial Diseases. It emphasizes the importance of considering a mitochondrial etiology in the diagnostic flowchart of a movement disorder.
JOURNAL OF NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Luca Marsili, Jennifer Sharma, Alberto J. Espay, Alice Migazzi, Elhusseini Abdelghany, Emily J. Hill, Kevin R. Duque, Matthew C. Hagen, Christopher D. Stephen, Gabor G. Kovacs, Anthony E. Lang, Marios Hadjivassiliou, Manuela Basso, Marcelo A. Kauffman, Andrea Sturchio
Summary: This study evaluated a case of a 60-year-old woman with a progressive dystonia-ataxia syndrome initially suspected to be Niemann-Pick disease Type C, but was later found to be progressive supranuclear palsy (PSP). Whole-exome sequencing revealed a new TGM6 variant associated with spinocerebellar ataxia type 35. The novel TGM6 variant reduced transglutaminase activity, suggesting a potential pathogenic role in the development of PSP pathology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Clinical Neurology
Malco Rossi, Moath Hamed, Jon Rodriguez-Antiguedad, Mario Cornejo-Olivas, Marianthi Breza, Katja Lohmann, Christine Klein, Rajasumi Rajalingam, Connie Marras, Bart P. van de Warrenburg
Summary: This article systematically reviewed the genotype-phenotype relationships and reevaluated the pathological range of repeat expansions in ATX-TBP. The study proposed new cutoff values for reduced penetrance (41-45 expanded repeats) and full penetrance (46-66 expanded repeats), which have important diagnostic and counseling implications and may guide future clinical trial protocols.
MOVEMENT DISORDERS
(2023)
Article
Immunology
Geraldine Blanchard-Rohner, Anna Peirolo, Ludivine Coulon, Christian Korff, Judit Horvath, Pierre R. Burkhard, Fabienne Gumy-Pause, Emmanuelle Ranza, Peter Jandus, Harpreet Dibra, Alexander Malcolm R. Taylor, Joel Fluss
Summary: Ataxia-telangiectasia (A-T) is a neurodegenerative and primary immunodeficiency disorder characterized by various symptoms. This study presents a case series highlighting the phenotypic variability of A-T and emphasizes the importance of early diagnosis of variant A-T and classical A-T.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Genetics & Heredity
Sara Biagiotti, Ambra Barone, Mattia Paolo Aliano, Giulia Federici, Marco Malatesta, Caterina Caputi, Silvia Soddu, Vincenzo Leuzzi, Luciana Chessa, Mauro Magnani
Summary: Most ATM variants associated with Ataxia Telangiectasia are classified as variants with uncertain significance. This study focused on a specific ATM variant found in Lebanese brothers, revealing it to be pathogenic even though it causes an atypical phenotype. Dexamethasone showed therapeutic potential on this and possibly other missense ATM variants.
FRONTIERS IN GENETICS
(2021)
Review
Biochemistry & Molecular Biology
Konrad Kaminiow, Izabella Rygula, Justyna Paprocka
Summary: There are over 150 inherited metabolic disorders that can present as ataxia in children. Neuroimaging studies and genetic studies are essential for diagnosis. Prompt treatment can positively influence neurodevelopment.
Article
Clinical Neurology
David Mengel, Andreas Traschuetz, Selina Reich, Alejandra Leyva-Gutierrez, Friedemann Bender, Stefan Hauser, Tobias B. Haack, Matthis Synofzik
Summary: The study reports the first de novo occurrence of a heterozygous STUB1 variant, providing additional qualitative evidence for autosomal-dominant STUB1-disease. The findings suggest that loss-of-function may underlie autosomal-dominant STUB1-disease, similar to its autosomal-recessive counterpart in terms of the affected neurological systems.
JOURNAL OF NEUROLOGY
(2021)
Article
Genetics & Heredity
Anna N. Senko, Rupert W. Overall, Jan Silhavy, Petr Mlejnek, Hana Malinska, Martina Huttl, Irena Markova, Klaus S. Fabel, Lu Lu, Ales Stuchlik, Robert W. Williams, Michal Pravenec, Gerd Kempermann
Summary: Neurogenesis in the adult hippocampus plays an important role in learning and memory in the healthy brain, but its regulation is disrupted in metabolic and neurodegenerative diseases. The molecular connections between neural stem cell activity, adult neurogenesis, and global metabolism are not well understood. In this study, unbiased systems genetics methods were used to analyze the genetic covariation between adult neurogenesis and metabolic phenotypes in a genetically diverse family of rat strains. The results identified a genetic locus on Chromosome 16 that is associated with both serum glucose levels and neuronal survival. Fine mapping of this locus revealed the Tti2 gene as a key player in regulating both neurogenesis and glucose metabolism. Mutations in Tti2 resulted in lower rates of neurogenesis and dysglycemia. These findings shed light on the genetic link between glucose metabolism and brain plasticity and have implications for understanding metabolic and neurological disorders in humans.
Review
Biochemistry & Molecular Biology
Goutham Narayanan Subramanian, Abrey Jie Yeo, Magtouf Hnaidi Gatei, David John Coman, Martin Francis Lavin
Summary: The ATM protein kinase has diverse functions in the cell, including protecting DNA, maintaining cellular homeostasis, and safeguarding against external and internal damage.
Article
Medicine, General & Internal
Federica Cavone, Susanna Cappelli, Alice Bonuccelli, Sofia D'Elios, Giorgio Costagliola, Diego Peroni, Alessandro Orsini, Rita Consolini
Summary: Ataxia telangiectasia (AT) is a rare disease characterized by neurodegenerative defects, immunodeficiency, and teleangiectasias. Ataxia is the main symptom of the disease.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Health Care Sciences & Services
Sharon A. McGrath-Morrow, Cynthia C. Rothblum-Oviatt, Jennifer Wright, Haley Schlechter, Maureen A. Lefton-Greif, Valerie A. Natale, Thomas O. Crawford, Howard M. Lederman
Summary: Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by progressive ataxia, oculocutaneous telangiectasias, and immune system impairment. Patients with A-T have an increased risk of malignancy, leading to premature death.
JOURNAL OF MULTIDISCIPLINARY HEALTHCARE
(2021)
Article
Clinical Neurology
David Pellerin, Carlo Wilke, Andreas Traschuetz, Sara Nagy, Riccardo Curro, Marie-Josee Dicaire, Hector Garcia-Moreno, Mathieu Anheim, Thomas Wirth, Jennifer Faber, Dagmar Timmann, Christel Depienne, Dan Rujescu, Jose Gazulla, Mary M. Reilly, Paola Giunti, Bernard Brais, Henry Houlden, Ludger Schoels, Michael Strupp, Andrea Cortese, Matthis Synofzik
Summary: Intronic GAA repeat expansions in the FGF14 gene are a common cause of cerebellar ataxia with polyneuropathy and/or bilateral vestibulopathy. They have potential phenotypic overlap with RFC1-related CANVAS syndrome. This study found a high frequency of FGF14 GAA repeat expansions in patients with an unexplained CANVAS-like phenotype.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Review
Clinical Neurology
Poonam Bhatia, Jennifer Heim, Patricia Cornejo, Lauren Kane, Jason Santiago, Michael C. Kruer
Summary: Opsoclonus-myoclonus-ataxia syndrome is a rare neuroimmunologic disorder that typically occurs in infants and toddlers, with about half of cases associated with neuroblastoma. The syndrome is characterized by saccadic intrusions, myoclonus, and behavioral abnormalities, and historically had poor long-term outcomes. Recent immunotherapy regimens offer hope for better outcomes in these children.
JOURNAL OF NEUROLOGY
(2022)
Article
Biology
Harvey Perez, May F. Abdallah, Jose Chavira, Angelina S. Norris, Martin T. Egeland, Karen L. Vo, Callan L. Buechsenschuetz, Valentina Sanghez, Jeannie L. Kim, Molly Pind, Kotoka Nakamura, Geoffrey G. Hicks, Richard A. Gatti, Joaquin Madrenas, Michelina Iacovino, Peter J. McKinnon, Paul J. Mathews
Summary: By introducing null mutations in both the Atm and Aptx genes in mice, researchers have created a novel mouse model that exhibits progressively severe ataxic phenotype and cerebellar molecular layer atrophy. The perturbations significantly alter the biophysical properties of cerebellar Purkinje neurons and their neural activity, correlating with cerebellar atrophy and ataxia over the animal's first year of life. Additionally, the double mutant mice also show a predisposition to cancer and immune abnormalities, resembling symptoms of A-T.
Article
Biochemistry & Molecular Biology
Jakub Czarny, Marta Andrzejewska, Olga Zajac-Spychala, Elzbieta Latos-Grazynska, Agata Pastorczak, Kamila Wypyszczak, Aleksandra Szczawinska-Poplonyk, Izabela Niewiadomska-Wojnalowicz, Agnieszka Wziatek, Patrycja Marciniak-Stepak, Michal Dopierala, Jadwiga Maldyk, Katarzyna Jonczyk-Potoczna, Katarzyna Derwich
Summary: Ataxia-telangiectasia (AT) is a rare genetic disorder characterized by DNA repair defect, chromosomal instability, and hypersensitivity to radiation. Successful clinical management of patients with AT is challenging due to poor treatment response, high toxicity, and the need to avoid radiation exposure. This case report describes a 7-year-old female patient with AT and LBCL with IRF4 rearrangement who achieved a favorable outcome through treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Marie Stoessel, Francois Lersy, Mylene Moris, Guillaume Bierry, Mathieu Anheim, Stephane Kremer, Sabrina Garnier-Kepka
Summary: This study evaluated the implementation of a dedicated MRI scanner for the management of patients with binocular diplopia in the emergency department. The results showed that the use of the MRI scanner improved the diagnostic performance of binocular diplopia and reduced patient's exposure to ionizing radiation without increasing turnaround time or emergency department length of stay.
JOURNAL OF NEURORADIOLOGY
(2023)
Article
Surgery
Pascale Mariani, Francois-Clement Bidard, Aurore Rampanou, Alexandre Houy, Vincent Servois, Toulsie Ramtohul, Gaelle Pierron, Marion Chevrier, Benjamin Renouf, Olivier Lantz, Sophie Gardrat, Anne Vincent-Salomon, Sergio Roman-Roman, Manuel Rodrigues, Sophie Piperno-Neumann, Nathalie Cassoux, Marc-Henri Stern, Shufang Renault
Summary: This study reports the detection rate and prognostic impact of circulating tumor DNA in patients undergoing surgical resection of liver metastases in uveal melanoma. If confirmed by further studies, this noninvasive biomarker could inform treatment decisions for liver metastases in uveal melanoma patients.
Meeting Abstract
Oncology
D. Rombaut, C. Lefevre, B. Farhat, S. Bondu, A. Letessier, A. Lesieur-Pasquier, D. Castillo-Guzman, M. Leduc, S. Hartono, V. Chesnais, R. Mangione, I. Boussaid, A. Houy, D. Bouscary, L. Willems, N. Chapuis, O. Kosmider, S. Park, S. Raynaud, T. Cluzeau, E. Clappier, P. Fenaux, L. Ades, R. Margueron, M. Wassef, S. Alsafadi, E. Solary, A. Constantinou, M. -H. Stern, B. Palancade, N. Droin, B. Miotto, F. Chedin, M. Fontenay
Article
Multidisciplinary Sciences
Petra ter Brugge, Sarah C. Moser, Ivan Bieche, Petra Kristel, Sabrina Ibadioune, Alexandre Eeckhoutte, Roebi de Bruijn, Eline van der Burg, Catrin Lutz, Stefano Annunziato, Julian de Ruiter, Julien Masliah Planchon, Sophie Vacher, Laura Courtois, Rania El-Botty, Ahmed Dahmani, Elodie Montaudon, Ludivine Morisset, Laura Sourd, Lea Huguet, Heloise Derrien, Fariba Nemati, Sophie Chateau-Joubert, Thibaut Larcher, Anne Salomon, Didier Decaudin, Fabien Reyal, Florence Coussy, Tatiana Popova, Jelle Wesseling, Marc-Henri Stern, Jos Jonkers, Elisabetta Marangoni
Summary: This study demonstrates that shallow HRD can predict the response to platinum-based chemotherapy in TNBC using patient-derived xenografts. Existing methods to identify HRD are controversial, and there is a medical need for predictive biomarkers. Evaluating the response to platinum agents in 55 TNBC patient-derived xenografts, the study found that the HRD status determined from whole genome sequencing can highly predict the response to platinum. Mutations in XRCC3 and ORC1 genes were also found to drive cisplatin response.
NATURE COMMUNICATIONS
(2023)
Review
Clinical Neurology
Poornima Jayadev Menon, Christelle Nilles, Laura Silveira-Moriyama, Ruiyi Yuan, Claudio M. de Gusmao, Alexander Muenchau, Miryam Carecchio, Steve Grossman, Gay Grossman, Aurelie Meneret, Emmanuel Roze, Tamara Pringsheim
Summary: This scoping review summarizes the available clinical literature on ADCY5-RMD. Patients with ADCY5-RMD experience permanent and/or paroxysmal hyperkinetic movements, which can be worsened by environmental triggers. Treatment options are limited, but caffeine, benzodiazepines, and deep brain stimulation have shown some effectiveness.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Clinical Neurology
Asya Ekmen, Mohamed Doulazmi, Aurelie Meneret, Prasanthi Jegatheesan, Anais Herve, Philippe Damier, Domitille Gras, Agathe Roubertie, Juliette Piard, Eugenie Mutez, Clement Tarrano, Quentin Welniarz, Marie Vidailhet, Yulia Worbe, Cecile Gallea, Emmanuel Roze
Summary: This study investigated the relationship between non-motor symptoms and health-related quality of life (HrQoL) in PKD patients caused by monoallelic pathogenic variants of PRRT2. The study found that non-motor manifestations were an important determinant of HrQoL and patients also experienced higher levels of self-esteem and stigmatization. The results have important implications for patient management and medical education about PKD.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Oncology
Pascale Mariani, Nouritza Torossian, Steven van Laere, Peter Vermeulen, Leanne de Koning, Sergio Roman-Roman, Olivier Lantz, Manuel Rodrigues, Marc-Henri Stern, Sophie Gardrat, Laetitia Lesage, Gabriel Champenois, Andre Nicolas, Alexandre Matet, Nathalie Cassoux, Vincent Servois, Emanuela Romano, Sophie Piperno-Neumann, Claire Lugassy, Raymond Barnhill
Summary: This study investigated the immune cell infiltrates in uveal melanoma liver metastases (UMLM) and found that CD68+ and CD163+ tumor-infiltrating macrophages, CD20+ peritumoral lymphocytes, and growth patterns were important prognostic factors.
BRITISH JOURNAL OF CANCER
(2023)
Article
Genetics & Heredity
Mathias Schwartz, Sabrina Ibadioune, Albain Chansavang, Sophie Vacher, Sandrine M. Caputo, Helene Delhomelle, Jennifer Wong, Khadija Abidallah, Virginie Moncoutier, Veronique Becette, Tatiana Popova, Voreak Suybeng, Antoine De Pauw, Marc-Henri Stern, Chrystelle Colas, Emmanuelle Mouret-Fourme, Dominique Stoppa-Lyonnet, Lisa Golmard, Ivan Bieche, Julien Masliah-Planchon
Summary: Mosaic BRCA1 promoter methylation is associated with an increased risk of early-onset breast cancer, triple-negative breast cancer, and ovarian cancer. This de novo event could contribute to hereditary breast/ovarian cancer pedigrees, especially in families with affected relatives showing high prevalence of BRCA1meth. Detection of BRCA1meth may indicate involvement of BRCA1 in tumorigenesis in affected probands.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Genetics & Heredity
Philip Bland, Harry Saville, Patty T. Wai, Lucinda Curnow, Gareth Muirhead, Jadwiga Nieminuszczy, Nivedita Ravindran, Marie Beatrix John, Somaieh Hedayat, Holly E. Barker, James Wright, Lu Yu, Ioanna Mavrommati, Abigail Read, Barrie Peck, Mark Allen, Patrycja Gazinska, Helen N. Pemberton, Aditi Gulati, Sarah Nash, Farzana Noor, Naomi Guppy, Ioannis Roxanis, Guy Pratt, Ceri Oldreive, Tatjana Stankovic, Samantha Barlow, Helen Kalirai, Sarah E. Coupland, Ronan Broderick, Samar Alsafadi, Alexandre Houy, Marc-Henri Stern, Stephen Pettit, Jyoti S. Choudhary, Syed Haider, Wojciech Niedzwiedz, Christopher J. Lord, Rachael Natrajan
Summary: SF3B1 mutations confer sensitivity to poly (ADP-ribose) polymerase inhibitors (PARPi). Mechanistically, this is independent of homologous recombination repair and instead relies on a defective replication stress response due to a reduction of the cyclin-dependent kinase 2 interacting protein (CINP). PARPi treatment of SF3B1 mutant (SF3B1(MUT)) tumors leads to replication stress induced by increased fork origin firing and culminates in cell cycle stalling. SF3B1 hotspot mutations are associated with a poor prognosis in several tumor types and lead to global disruption of canonical splicing.
Article
Cell Biology
David Gentien, Elnaz Saberi-Ansari, Nicolas Servant, Ariane Jolly, Pierre de la Grange, Fariba Nemati, Geraldine Liot, Simon Saule, Aurelie Teissandier, Deborah Bourc'his, Elodie Girard, Jennifer Wong, Julien Masliah-Planchon, Erkan Narmanli, Yuanlong Liu, Emma Torun, Rebecca Goulancourt, Manuel Rodrigues, Laure Villoing Gaude, Cecile Reyes, Mateo Bazire, Thomas Chenegros, Emilie Henry, Audrey Rapinat, Mylene Bohec, Sylvain Baulande, Radhia M'kacher, Eric Jeandidier, Andre Nicolas, Giovanni Ciriello, Raphael Margueron, Didier Decaudin, Nathalie Cassoux, Sophie Piperno-Neumann, Marc-Henri Stern, Johan Harmen Gibcus, Job Dekker, Edith Heard, Sergio Roman-Roman, Joshua J. Waterfall
Summary: Through comprehensive multi-omics characterization, we identified genomic instability as a hallmark of uveal melanoma (UM) and confirmed the recurrent deletion in the BAP1 promoter associated with high risk of metastasis in UM patients. We also discovered the upregulation of PRAME as an independent prognostic biomarker and a potential therapeutic target in UM.
Article
Hematology
Audrey Petit, Benedicte Neven, Victoria Min, Nizar Mahlaoui, Despina Moshous, Martin Castelle, Maya Allouche, Arthur Sterin, Sandrine Visentin, Paul Saultier, Mohamed Boucekine, Alaa Mustafa Shawket, Capucine Picard, Pascal Auquier, Gerard Michel, Alain Fischer, Vincent Barlogis
Summary: The survival rate after hematopoietic stem cell transplantation for inborn errors of immunity has improved considerably, but many patients still experience poor health status and impaired quality of life. Abnormal graft function and chronic graft-versus-host disease are correlated with poor health and very poor health, which in turn directly affect the patients' HRQoL. Further studies are needed to examine the long-term impact of transplant procedure improvements on health status and HRQoL.
TRANSPLANTATION AND CELLULAR THERAPY
(2023)
Meeting Abstract
Oncology
Phil Bland, Harry Saville, Abigail Read, Patty Wai, Gareth Muirhead, Lucinda Curnow, Jadwiga Nieminuszczy, Nivedita Ravindran, Marie John, Somaieh Hedayat, Holly Barker, James Wright, Lu Yu, Ioanna Mavrommati, Barrie Peck, Mark Allen, Patrycja Gazinska, Helen Pemberton, Aditi Gulati, Sarah Nash, Farzana Noor, Naomi Guppy, Ioannis Roxanis, Samantha Barlow, Helen Kalirai, Sarah Coupland, Ronan Broderick, Samar Alsafadi, Alexandre Houy, Marc-Henri Stern, Stephen Pettit, Jyoti Choudhary, Syed Haider, Wojciech Niedzwiedz, Christopher Lord, Rachael Natrajan
Article
Ophthalmology
Sen Ma, Ruben V. Huis In't Veld, Alexander Houy, Marc-Henri Stern, Cadmus Rich, Ferry A. Ossendorp, Martine J. Jager
Summary: The virus-like drug conjugate AU-011 shows potential in inducing immunogenic cell death in uveal melanoma cell lines, which may lead to systemic immune responses and suggests its potential for combination with immunotherapy.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
Article
Oncology
Marie-Charlotte Villy, Anais Le Ven, Marine Le Mentec, Julien Masliah-Planchon, Alexandre Houy, Ivan Bieche, Sophie Vacher, Anne Vincent-Salomon, Catherine Dubois d'Enghien, Mathias Schwartz, Sophie Piperno-Neumann, Alexandre Matet, Denis Malaise, Virginie Bubien, Alain Lortholary, Amal Ait Omar, Mathias Cavaille, Dominique Stoppa-Lyonnet, Nathalie Cassoux, Marc-Henri Stern, Manuel Rodrigues, Lisa Golmard, Chrystelle Colas
Summary: This study finds that monoallelic germline pathogenic variants in the MBD4 gene are associated with susceptibility to uveal melanoma and breast cancer among other cancer types. Further genetic testing and molecular tumor analyses are necessary to better understand the tumor spectrum and estimate the risk associated with this predisposition.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Biochemistry & Molecular Biology
Celine Callens, Manuel Rodrigues, Adrien Briaux, Eleonore Frouin, Alexandre Eeckhoutte, Eric Pujade-Lauraine, Victor Renault, Dominique Stoppa-Lyonnet, Ivan Bieche, Guillaume Bataillon, Lucie Karayan-Tapon, Tristan Rochelle, Florian Heitz, Sabrina Chiara Cecere, Maria Jesus Rubio Perez, Christoph Grimm, Trine Jakobi Nottrup, Nicoletta Colombo, Ignace Vergote, Kan Yonemori, Isabelle Ray-Coquard, Marc-Henri Stern, Tatiana Popova
Summary: The bevacizumab/olaparib maintenance regimen has been approved for first-line treatment of BRCA-mutated and HRD high-grade advanced ovarian cancer, based on the significantly improved progression-free survival compared to bevacizumab alone. In this study, a new test called shallowHRDv2 was developed as an alternative to MyChoice for HRD detection. The results show that shallowHRDv2 is a high-performing, clinically validated, and cost-effective test for HRD detection.