Article
Genetics & Heredity
Manuela Morleo, Rossella Venditti, Evangelos Theodorou, Lauren C. Briere, Marion Rosello, Alfonsina Tirozzi, Roberta Tammaro, Nour Al-Badri, Frances A. High, Elena Undiagnosed Dis NetworK, Luigi Telethon Undiagnosed Dis Program, Elena Putti, Luigi Ferrante, Viviana Cetrangolo, Annalaura Torella, Melissa A. Walker, Romano Tenconi, Maria Iascone, Davide Mei, Renzo Guerrini, Jasper van der Smagt, Hester Y. Kroes, Koen L. I. van Gassen, Muhammad Bilal, Muhammad Umair, Veronica Pingault, Tania Attie-Bitach, Jeannine Amiel, Resham Ejaz, Lance Rodan, Marcella Zollino, Pankaj B. Agrawal, Filippo Del Bene, Vincenzo Nigro, David A. Sweetser, Brunella Franco
Summary: Phosphoinositides (PIs) are membrane phospholipids that control membrane composition and play key roles in cellular processes. Mutations in PIP5K1C gene cause a neurodevelopmental disorder with increased PI(4,5)P2 production and dysfunction in PI-signaling. This disorder leads to intellectual disability, developmental delay, microcephaly, seizures, visual abnormalities, and dysmorphic features.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Cell Biology
Amanda Koire, Panagiotis Katsonis, Young Won Kim, Christie Buchovecky, Stephen J. Wilson, Olivier Lichtarge
Summary: Applying an evolutionary action method to analyze de novo missense variants in individuals with autism spectrum disorder (ASD), this study identified genes and pathways connected to ASD pathogenesis and phenotypic impact. The missense variants involved pathways related to axonogenesis, synaptic transmission, and neuro-development, with predicted fitness impact correlating with the IQ of individuals with ASD. This approach could be applied to identify genes contributing to shared phenotypes in other complex diseases by integrating missense variants across patient cohorts.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Xiangbin Jia, Shujie Zhang, Senwei Tan, Bing Du, Mei He, Haisong Qin, Jia Chen, Xinyu Duan, Jingsi Luo, Fei Chen, Luping Ouyang, Jian Wang, Guodong Chen, Bin Yu, Ge Zhang, Zimin Zhang, Yongqing Lyu, Yi Huang, Jian Jiao, Jin Yun Helen Chen, Kathryn J. Swoboda, Emanuele Agolini, Antonio Novelli, Chiara Leoni, Giuseppe Zampino, Gerarda Cappuccio, Nicola Brunetti-Pierri, Benedicte Gerard, Emmanuelle Ginglinger, Julie Richer, Hugh McMillan, Alexandre White-Brown, Kendra Hoekzema, Raphael A. Bernier, Evangeline C. Kurtz-Nelson, Rachel K. Earl, Claartje Meddens, Marielle Alders, Meredith Fuchs, Roseline Caumes, Perrine Brunelle, Thomas Smol, Ryan Kuehl, Debra-Lynn Day-Salvatore, Kristin G. Monaghan, Michelle M. Morrow, Evan E. Eichler, Zhengmao Hu, Ling Yuan, Jieqiong Tan, Kun Xia, Yiping Shen, Hui Guo
Summary: This study reports a newly identified neurodevelopmental disorder and suggests the importance of stress granules (SGs) in its pathology. By studying mice and analyzing data from a large number of patients, the researchers found that genetic variants in genes related to SGs were associated with the disorder. These findings provide significant insights into the underlying mechanisms of neurodevelopmental disorders.
Article
Genetics & Heredity
Natalie B. Tan, Alistair T. Pagnamenta, Matteo P. Ferla, Jonathan Gadian, Brian H. Y. Chung, Marcus C. Y. Chan, Jasmine L. F. Fung, Edwin Cook, Stephen Guter, Felix Boschann, Andre Heinen, Jens Schallner, Cyril Mignot, Boris Keren, Sandra Whalen, Catherine Sarret, Dana Mittag, Laurie Demmer, Rachel Stapleton, Ken Saida, Naomichi Matsumoto, Noriko Miyake, Ruth Sheffer, Hagar Mor-Shaked, Christopher P. Barnett, Alicia B. Byrne, Hamish S. Scott, Alison Kraus, Gerarda Cappuccio, Nicola Brunetti-Pierri, Raffaele Iorio, Fabiola Di Dato, Lynn S. Pais, Alison Yeung, Tiong Y. Tan, Jenny C. Taylor, John Christodoulou, Susan M. White
Summary: This study confirmed GNB2 as a neurodevelopmental disease gene, with missense variants causing a congenital disorder with variable syndromic features. The identified variants weaken the interaction with the G alpha subunit and broaden the spectrum of multisystem phenotypes associated with genes encoding G-proteins.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Genetics & Heredity
Zelha Nil, Ashish R. Deshwar, Yan Huang, Scott Barish, Xi Zhang, Sanaa Choufani, Polona Le Quesne Stabej, Ian Hayes, Patrick Yap, Chad Haldeman-Englert, Carolyn Wilson, Trine Prescott, Kristian Tveten, Arve Vollo, Devon Haynes, Patricia G. Wheeler, Jessica Zon, Cheryl Cytrynbaum, Rebekah Jobling, Moira Blyth, Siddharth Banka, Alexandra Afenjar, Cyril Mignot, Florence Robin-Renaldo, Boris Keren, Oguz Kanca, Xiao Mao, Daniel J. Wegner, Kathleen Sisco, Marwan Shinawi, Michael F. Wangler, Rosanna Weksberg, Shinya Yamamoto, Gregory Costain, Hugo J. Bellen
Summary: Misregulation of histone lysine methylation, particularly caused by mutations in the DOT1L gene, is associated with human developmental disorders. This study identified seven different de novo heterozygous missense variants in DOT1L in nine unrelated individuals, leading to elevated levels of histone methylation and developmental delays in humans. Functional studies performed in fruit flies and human cells confirmed the pathogenicity of these variants. The findings highlight the importance of DOT1L in human development and its association with Mendelian diseases.
AMERICAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Meer Jacob Rahimi, Nicole Urban, Meret Wegler, Heinrich Sticht, Michael Schaefer, Bernt Popp, Frank Gaunitz, Manuela Morleo, Vincenzo Nigro, Silvia Maitz, Grazia M. S. Mancini, Claudia Ruivenkamp, Eun-Kyung Suk, Tobias Bartolomaeus, Andreas Merkenschlager, Daniel Koboldt, Dennis Bartholomew, Alexander P. A. Stegmann, Margje Sinnema, Irma Duynisveld, Ramona Salvarinova, Simone Race, Bert B. A. de Vries, Aurelien Trimouille, Sophie Naudion, Daphna Marom, Uri Hamiel, Noa Henig, Florence Demurger, Nils Rahner, Enrika Bartels, J. Austin Hamm, Abbey M. Putnam, Richard Person, Rami Abou Jamra, Henry Oppermann
Summary: Variants in the ATP2B1 gene lead to neurodevelopmental disorders characterized by global development delay, autism, seizures, and limb abnormalities. These variants result in a significant decrease in the export capacity of calcium ions and incorrect cellular localization of ATP2B1.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Multidisciplinary Sciences
Malte Zorn, Jirko Kuehnisch, Sebastian Bachmann, Wenke Seifert
Summary: This study investigated the pathogenic effect of missense variants in the VPS13B gene on Cohen syndrome through clinical patient information, in silico predictions, and in vitro testing. The study found that 6 out of 10 missense variants were likely pathogenic, providing insights into the pathomechanisms of Cohen syndrome.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Xi Luo, Kelly Schoch, Sharayu Jangam, Venkata Hemanjani Bhavana, Hillary K. Graves, Sujay Kansagra, Joan M. Jasien, Nicholas Stong, Boris Keren, Cyril Mignot, Claudia Ravelli, Hugo J. Bellen, Michael F. Wangler, Vandana Shashi, Shinya Yamamoto
Summary: This study identified two individuals with rare de novo missense variants in the Polycomb group gene RNF2, leading to a new and recognizable genetic disorder characterized by severe physical and intellectual disabilities. Structural analysis suggested that the variants likely impact the interaction between RNF2 and other proteins, and functional data in Drosophila supported these variants behaving as loss-of-function alleles in vivo. These findings highlight the significance of chromatin regulators, such as PcG genes, in Mendelian disorders.
HUMAN MOLECULAR GENETICS
(2021)
Article
Genetics & Heredity
Yukiko Kuroda, Aiko Iwata-Otsubo, Kerith-Rae Dias, Suzanna E. L. Temple, Koji Nagao, Lachlan De Hayr, Ying Zhu, Shin-Ya Isobe, Gohei Nishibuchi, Sarah K. Fiordaliso, Yuki Fujita, Alyssa L. Rippert, Samuel W. Baker, Marco L. Leung, Daniel C. Koboldt, Adele Harman, Beth A. Keena, Izumi Kazama, Gopinath Musuwadi Subramanian, Kandamurugu Manickam, Betsy Schmalz, Maeson Latsko, Elaine H. Zackai, Matt Edwards, Carey-Anne Evans, Matthew C. Dulik, Michael F. Buckley, Toshihide Yamashita, W. Timothy O'Brien, Robert J. Harvey, Chikashi Obuse, Tony Roscioli, Kosuke Izumi
Summary: This study identified heterozygous de novo variants in the CBX1 gene, encoding HP1β, as a cause of a novel syndromic neurodevelopmental disorder. In vitro cellular assays, neurobehavioral and cytological analyses of neuronal cells, and mouse models confirmed the pathogenicity of the identified variants. The disruption of HP1β chromatin binding during neurocognitive development contributes to developmental disabilities.
GENETICS IN MEDICINE
(2023)
Editorial Material
Clinical Neurology
Maike F. Dohrn, Adriana P. Rebelo, Siddharth Srivastava, Gerarda Cappuccio, Robert Smigiel, Alka Malhotra, Donald Basel, Ingrid van de Laar, Rinze Frederik Neuteboom, Coranne Aarts-Tesselaar, Sonal Mahida, Nicola Brunetti-Pierri, Ryan J. Taft, Stephan Zuchner
Summary: This study identified five unrelated children with intellectual disability, spasticity, and peripheral neuropathy carrying heterozygous ATP1A1 variants. The variants led to loss of ATPase function and were associated with additional symptoms such as sensory loss, sleep disturbances, and seizures. These de novo variants had high pathogenicity prediction scores and replicated the haploinsufficiency mechanism of disease.
Article
Genetics & Heredity
Olivier Ariste, Pierre de la Grange, Reiner A. Veitia
Summary: Clonal hematopoiesis refers to the abnormal expansion of a hematopoietic stem cell with advantageous somatic variants. A survey found that some common gene mutations have higher frequencies in various populations and are enriched in specific populations. The age distribution of individuals with these variants suggests a potential involvement in clonal hematopoiesis, and the variant allele frequencies in blood DNA of elderly individuals are lower than expected. This can result in misclassification of somatic variants in cancer-predisposition genes, which has consequences for affected individuals and their families.
Article
Genetics & Heredity
Volkan Okur, Zefu Chen, Liesbeth Vossaert, Sandra Peacock, Jill Rosenfeld, Lina Zhao, Haowei Du, Emily Calamaro, Amanda Gerard, Sen Zhao, Jill Kelsay, Ashley Lahr, Chloe Mighton, Hillary M. Porter, Amy Siemon, Josh Silver, Shayna Svihovec, Chin-To Fong, Christina L. Grant, Jordan Lerner-Ellis, Kandamurugu Manickam, Suneeta Madan-Khetarpal, Shawn E. McCandless, Chantal F. Morel, G. Bradley Schaefer, Elizabeth M. Berry-Kravis, Ryan Gates, Natalia Gomez-Ospina, Guixing Qiu, Terry Jianguo Zhang, Zhihong Wu, Linyan Meng, Pengfei Liu, Daryl A. Scott, James R. Lupski, Christine M. Eng, Nan Wu, Bo Yuan
Summary: The histone H3 variant H3.3, encoded by genes H3-3A and H3-3B, plays a role in congenital disorders and can replace canonical isoforms H3.1 and H3.2. Studies have found that H3.3 variants are associated with various disease phenotypes, including global developmental delay, short stature, and visual impairment.
NPJ GENOMIC MEDICINE
(2021)
Article
Clinical Neurology
Serena Galosi, Ban H. Edani, Simone Martinelli, Hana Hansikova, Erik A. Eklund, Caterina Caputi, Laura Masuelli, Nicole Corsten-Janssen, Myriam Srour, Renske Oegema, Danielle G. M. Bosch, Colin A. Ellis, Louise Amlie-Wolf, Andrea Accogli, Isis Atallah, Luisa Averdunk, Kristin W. Baranano, Roberto Bei, Irene Bagnasco, Alfredo Brusco, Scott Demarest, Anne-Sophie Alaix, Carlo Di Bonaventura, Felix Distelmaier, Frances Elmslie, Ziv Gan-Or, Jean-Marc Good, Karen Gripp, Erik-Jan Kamsteeg, Ellen Macnamara, Carlo Marcelis, Noelle Mercier, Joseph Peeden, Simone Pizzi, Luca Pannone, Marwan Shinawi, Camilo Toro, Nienke E. Verbeek, Sunita Venkateswaran, Patricia G. Wheeler, Lucie Zdrazilova, Rong Zhang, Giovanna Zorzi, Renzo Guerrini, William C. Sessa, Dirk Lefeber, Marco Tartaglia, Fadi F. Hamdan, Kariona A. Grabinska, Vincenzo Leuzzi
Summary: This study investigated the variants in the DHDDS gene and found that they are associated with a new neurodegenerative disorder characterized by symptoms such as neurodevelopmental disorders, epilepsy, myoclonus, and cognitive decline. The study also revealed dysfunctional lysosomal enzymatic scavenger machinery.
Article
Genetics & Heredity
Maria Lucia Cediel, Michal Stawarski, Xavier Blanc, Lenka Noskova, Martin Magner, Konrad Platzer, Janina Gburek-Augustat, Dustin Baldridge, John N. Constantino, Emmanuelle Ranza, Bernhard Bettler, Stylianos E. Antonarakis
Summary: GABA(B) receptors are responsible for neuronal inhibition in the central nervous system. Variants in GABBR2 have been associated with certain phenotypes, while no phenotypes have been established for GABBR1 variants. This study identified four GABBR1 variants in individuals with motor and/or language delay, and functional characterization revealed their impact on GABA potency and efficacy, providing insights into disease severity and potential therapeutic strategies.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Biology
Lydie Burglen, Evelien Van Hoeymissen, Leila Qebibo, Magalie Barth, Newell Belnap, Felix Boschann, Christel Depienne, Katrien De Clercq, Andrew G. L. Douglas, Mark P. Fitzgerald, Nicola Foulds, Catherine Garel, Ingo Helbig, Katharina Held, Denise Horn, Annelies Janssen, Angela M. Kaindl, Vinodh Narayanan, Christina Prager, Mailys Rupin-Mas, Alexandra Afenjar, Siyuan Zhao, Vincent Th Ramaekers, Sarah M. Ruggiero, Simon Thomas, Stephanie Valence, Lionel Van Maldergem, Tibor Rohacs, Diana Rodriguez, David Dyment, Thomas Voets, Joris Vriens
Summary: TRPM3 is a plasma membrane cation channel that is sensitive to temperature and neurosteroids and is expressed in various types of cells. Rare variants in TRPM3 have been found in individuals with developmental and epileptic encephalopathy, but the connection between TRPM3 activity and neurological disorders is not well understood. In this study, we identified additional heterozygous missense variants in TRPM3 in 10 patients with a range of neurodevelopmental symptoms. These variants cause a gain-of-function phenotype, leading to increased channel activity and altered calcium levels in cells. Treatment with the TRPM3 antagonist primidone reduced the increased channel activity, suggesting that TRPM3 antagonists could be a potential therapy for these disorders.
Editorial Material
Pediatrics
Angelica Bibiana Delogu, Rita Blandino, Chiara Leoni, Marco Tartaglia, Giuseppe Zampino
PEDIATRIC RESEARCH
(2023)
Article
Genetics & Heredity
Marcello Niceta, Simone Pizzi, Francesca Inzana, Angela Peron, Somayeh Bakhtiari, Mathilde Nizon, Jonathan Levy, Cecilia Mancini, Benjamin Cogne, Francesca Clementina Radio, Emanuele Agolini, Dario Cocciadiferro, Antonio Novelli, Mustafa A. Salih, Maria Paola Recalcati, Rosangela Arancio, Marianne Besnard, Anne-Claude Tabet, Michael C. Kruer, Manuela Priolo, Bruno Dallapiccola, Marco Tartaglia
Summary: CNOT2 haploinsufficiency is the underlying cause of a rare neurodevelopmental disorder called Intellectual Developmental disorder with NAsal speech, Dysmorphic Facies, and variable Skeletal anomalies (IDNADFS, OMIM 618608). This disorder shares clinical similarities with chromosome 12q15 deletion syndrome, suggesting that CNOT2 haploinsufficiency plays a significant role in the latter. CNOT2 is a member of the CCR4-NOT complex, which regulates various cellular processes. The clinical profile of IDNADFS remains incompletely understood due to the limited number of reported cases.
Article
Genetics & Heredity
Richard H. van Jaarsveld, Jack Reilly, Marie-Claire Cornips, Michael A. Hadders, Emanuele Agolini, Priyanka Ahimaz, Kwame Anyane-Yeboa, Severine Audebert Bellanger, Ellen van Binsbergen, Marie-Jose van den Boogaard, Elise Brischoux-Boucher, Raymond C. Caylor, Andrea Ciolfi, Ton A. J. van Essen, Paolo Fontana, Saskia Hopman, Maria Iascone, Margaret M. Javier, Erik-Jan Kamsteeg, Jennifer Kerkhof, Jun Kido, Hyung-Goo Kim, Tjitske Kleefstra, Fortunato Lonardo, Abbe Lai, Dorit Lev, Michael A. Levy, M. E. Suzanne Lewis, Angie Lichty, Marcel M. A. M. Mannens, Naomichi Matsumoto, Idit Maya, Haley McConkey, Andre Megarbane, Vincent Michaud, Evelina Miele, Marcello Niceta, Antonio Novelli, Roberta Onesimo, Rolph Pfundt, Bernt Popp, Eloise Prijoles, Raissa Relator, Sylvia Redon, Dmitrijs Rots, Karen Rouault, Ken Saida, Jolanda Schieving, Marco Tartaglia, Romano Tenconi, Kevin Uguen, Nienke Verbeek, Christopher A. Walsh, Keren Yosovich, Christopher J. Yuskaitis, Giuseppe Zampino, Bekim Sadikovic, Marielle Alders, Renske Oegema
Summary: This study collected data on individuals with heterozygous KDM2B variants and used methylation arrays to identify a KDM2B-associated epigenetic signature. The study found that pathogenic heterozygous variants in KDM2B are associated with neurodevelopmental disorders (NDDs) and identified the CxxC domain as a mutational hotspot. The results also showed that the KDM2B episignature can be identified in the context of a dual molecular diagnosis in multiple individuals.
GENETICS IN MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Elisabetta Flex, Shahad Albadri, Francesca Clementina Radio, Serena Cecchetti, Antonella Lauri, Manuela Priolo, Marta Kissopoulos, Giovanna Carpentieri, Giulia Fasano, Martina Venditti, Valentina Magliocca, Emanuele Bellacchio, Carrie L. Welch, Paolo C. Colombo, Stephanie M. Kochav, Richard Chang, Rebekah Barrick, Marina Trivisano, Alessia Micalizzi, Rossella Borghi, Elena Messina, Cecilia Mancini, Simone Pizzi, Flavia De Santis, Marion Rosello, Nicola Specchio, Claudia Compagnucci, Kirsty McWalter, Wendy K. Chung, Filippo Del Bene, Marco Tartaglia
Summary: Kinesins are motor proteins involved in intracellular transport, contributing to key cellular processes. Pathogenic variants in kinesin-encoding genes underlie human diseases. Understanding the significance of these variants is important for better understanding the cellular transport system and its relationship with diseases.
HUMAN MOLECULAR GENETICS
(2023)
Article
Genetics & Heredity
Mathis Hildonen, Marco Ferilli, Tina Duelund Hjortshoj, Morten Duno, Lotte Risom, Mads Bak, Jakob Ek, Rikke. S. S. Moller, Andrea Ciolfi, Marco Tartaglia, Zeynep Tumer
Summary: Disease-specific DNA methylation patterns (DNAm signatures) have been established for an increasing number of genetic disorders and can be used as a valuable tool for classification of genetic variants of uncertain significance (VUS). This study demonstrates the clinical utility of a robust DNAm signature and highlights the importance of data sharing for improved diagnosis of rare genetic disorders.
Article
Biochemistry & Molecular Biology
Francesca Piceci-Sparascio, Lucia Micale, Barbara Torres, Valentina Guida, Federica Consoli, Isabella Torrente, Annamaria Onori, Emanuela Frustaci, Maria Cecilia D'Asdia, Francesco Petrizzelli, Laura Bernardini, Cecilia Mancini, Fiorenza Soli, Dario Cocciadiferro, Daniele Guadagnolo, Gioia Mastromoro, Carolina Putotto, Franco Fontana, Nicola Brunetti-Pierri, Antonio Novelli, Antonio Pizzuti, Bruno Marino, Maria Cristina Digilio, Tommaso Mazza, Bruno Dallapiccola, Victor Luis Ruiz-Perez, Marco Tartaglia, Marco Castori, Alessandro De Luca
Summary: Deleterious variants of the DYNC2H1 gene are associated with a wide range of skeletal ciliopathies. Targeted parallel sequencing was used to analyze 25 families with unresolved molecular diagnoses. Deleterious DYNC2H1 variants were identified in six sporadic patients and two monozygotic twins. The clinical phenotypes displayed a variety of skeletal ciliopathy disorders, including EvC, mixed ATD/EvC, and short rib-polydactyly/EvC.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Anne-Sophie Denomme-Pichon, Leslie Matalonga, Elke de Boer, Adam Jackson, Elisa Benetti, Siddharth Banka, Ange-Line Bruel, Andrea Ciolfi, Jill Clayton-Smith, Bruno Dallapiccola, Yannis Duffourd, Kornelia Ellwanger, Chiara Fallerini, Christian Gilissen, Holm Graessner, Tobias B. Haack, Marketa Havlovicova, Alexander Hoischen, Nolwenn Jean-Marcais, Tjitske Kleefstra, Estrella Lopez-Martin, Milan Macek, Maria Antonietta Mencarelli, Sebastien Moutton, Rolph Pfundt, Simone Pizzi, Manuel Posada, Francesca Clementina Radio, Alessandra Renieri, Caroline Rooryck, Lukas Ryba, Hana Safraou, Martin Schwarz, Marco Tartaglia, Christel Thauvin-Robinet, Julien Thevenon, Frederic Tran Mau-Them, Aurelien Trimouille, Pavel Votypka, Bert B. A. de Vries, Marjolein H. Willemsen, Birte Zurek, Alain Verloes, Christophe Philippe, Antonio Vitobello, Lisenka E. L. M. Vissers, Laurence Faivre
Summary: Within the Solve-RD project, the European Reference Network aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. The results of the ClinVar low-hanging fruit reanalysis, reasons for previous analysis failure, and lessons learned are presented.
GENETICS IN MEDICINE
(2023)
Review
Genetics & Heredity
Sanna Gudmundsson, Colleen M. Carlston, Anne O'Donnell-Luria
Summary: Reference population databases such as gnomAD have improved our ability to interpret the human genome, but clonal hematopoiesis (CH) poses challenges in variant interpretation. Somatic variants associated with CH can affect variant frequencies and downstream filtering. Filtering variants or genes associated with CH may inadvertently exclude true germline variants and cause Mendelian conditions. Here, we provide insights and recommendations for interpreting population variant data in genes affected by CH, specifically focusing on 36 established CH genes associated with neurodevelopmental conditions.
Article
Clinical Neurology
Audrey Riquet, Pierre Cleuziou, Valentine Floret, Francois Quesque, Sabine Defoort, Thomas Smol
Summary: This article reports a case of a two-month-old infant with a de novo pathogenic variation of CACNA1G who presented with paroxysmal tonic upgaze (PTU) associated with congenital ataxia and other periodic neurological manifestations. Detailed video documentations of PTU, paroxysmal torticollis, and ataxia in a patient with a CACNA1G mutation are provided, allowing a better understanding of the underlying mechanisms of PTU and suggesting potential new avenues for clinical treatments.
PEDIATRIC NEUROLOGY
(2023)
Article
Clinical Neurology
Lorenzo Ricci, Eleonora Tamilia, Mattia Mercier, Chiara Pepi, Giusy Carfi-Pavia, Alessandro De Benedictis, Giovanni Assenza, Vincenzo Di Lazzaro, Federico Vigevano, Nicola Specchio, Luca de Palma
Summary: This study aimed to evaluate whether ictal phase-amplitude coupling (PAC) could be used as a preoperative biomarker for Focal Cortical Dysplasia (FCD) subtypes. It was found that the strength of ictal PAC was significantly higher in patients with FCD type II compared to type I, only on SOZ electrodes. Pre-ictal PAC on SOZ electrodes predicted FCD histopathology with a classification accuracy > 0.9.
CLINICAL NEUROPHYSIOLOGY
(2023)
Article
Clinical Neurology
Simona Balestrini, Viola Doccini, Sabrina Giometto, Ersilia Lucenteforte, Salvatore De Masi, Elisa Giarola, Isabella Brambilla, Federica Pieroni, Marco Perulli, Domenica Battaglia, Nicola Specchio, Francesca Ragona, Tiziana Granata, Simona Pellacani, Annarita Ferrari, Carla Marini, Sara Matricardi, Elisabetta Cesaroni, Lucio Giordano, Patrizia Accorsi, Vittorio Sciruicchio, Paolo Tinuper, Tullio Messana, Angelo Russo, Dario Pruna, Margherita Nosadini, Valentina De Giorgis, Davide Caputo, Serena Residras Collaboration Grp, Serena Pellegrin, Tommaso Lo Barco, Francesca Darra, Bernardo Dalla Bernardina, Renzo Guerrini
Summary: We present the Residras registry, a comprehensive resource for Dravet syndrome and other phenotypes related to SCN1A mutations. The registry collects standardized data from pediatric and adult patients in 24 Italian expert centers. The data includes demographic information, clinical outcomes, and mortality rates. The registry has currently enrolled 281 individuals with Dravet syndrome and a confirmed SCN1A mutation, and has observed changes in cognitive function, behavioral disorders, language, and intellectual disability over a 5-year follow-up period. The Residras registry provides valuable data for research, clinical trials, and monitoring the natural history of Dravet syndrome.
Article
Genetics & Heredity
Lorenzo Sinibaldi, Giacomo Garone, Alessandra Mandarino, Giancarlo Iarossi, Laura Chioma, Marialisa Dentici, Giuseppe Merla, Emanuele Agolini, Alessia Micalizzi, Cecilia Mancini, Marcello Niceta, Marina Macchiaiolo, Daria Diodato, Roberta Onesimo, Rita Blandino, Angelica Bibiana Delogu, Gabriella De Rosa, Valentina Trevisan, Mariella Iademarco, Giuseppe Zampino, Marco Tartaglia, Antonio Novelli, Andrea Bartuli, Maria Cristina Digilio, Giulio Calcagni
Summary: Variants in the CTNNB1 gene are associated with neurodevelopmental disorder, visual defects, and congenital heart anomalies. A study on 19 NEDSDV patients found that 5 of them had congenital heart defects, highlighting the importance of cardiac examination in NEDSDV clinical management.
Correction
Biochemistry & Molecular Biology
Alicia B. Byrne, Peer Arts, Thuong T. Ha, Karin S. Kassahn, Lynn S. Paris, Anne O'Donnell-Luria, Milena Babic, Mahalia S. B. Frank, Jinghua Feng, Paul Wang, David M. Lawrence, Leila Eshraghi, Luis Arriola, John Toubia, Hung Nguyen, George McGillivray, Jason Pinner, Fiona McKenzie, Rebecca Morrow, Jill Lipsett, Nick Manton, T. Yee Khong, Lynette Moore, Jan E. Liebelt, Andreas W. Schreiber, Sarah L. King-Smith, Tristan S. E. Hardy, Matilda R. Jackson, Christopher P. Barnett, Hamish S. Scott, Broad Inst Ctr Mendelian Genomics, Genomic Autopsy Study Res Network
Article
Behavioral Sciences
Rossella Borghi, Marina Trivisano, Nicola Specchio, Marco Tartaglia, Claudia Compagnucci
Summary: Dominant mutations in CAMK2B cause a neurodevelopmental disorder characterized by delayed development, intellectual disability, hypotonia, and behavioral abnormalities, with no targeted therapies available.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)