Article
Clinical Neurology
Saul A. Frankford, Lena C. O'Flynn, Kristina Simonyan
Summary: This study investigated sensory processing in auditory and olfactory domains in patients with laryngeal dystonia, and found that auditory temporal discrimination and olfactory function are likely not endophenotypic markers of the disorder.
JOURNAL OF NEUROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Chi-Jing Choong, Hideki Mochizuki, Cesar Borlongan
Summary: Mitochondrial dysregulation is strongly associated with the pathogenesis of Parkinson's disease (PD), with mutated genes affecting mitochondrial features. Disruption of mitochondrial quality control and abnormal secretion of mitochondrial contents play a role in PD, and circulating mitochondrial DNAs can elicit inflammatory response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biology
Filipa Barroso Goncalves, Vanessa Alexandra Morais
Summary: Mitochondria are highly dynamic organelles crucial for energy production. Recent studies have shown their role in maintaining cell homeostasis and regulating cell fate through mitochondrial quality control pathways. PINK1, a key player in these pathways, interacts with substrates to regulate mitochondrial functions and plays a role in mitochondrial clearance, maintenance, and homeostasis, with implications in Parkinson's disease.
Article
Biochemistry & Molecular Biology
Zhi Dong Zhou, Wuan Ting Saw, Patrick Ghim Hoe Ho, Zhi Wei Zhang, Li Zeng, Ya Yin Chang, Alfred Xu Yang Sun, Dong Rui Ma, Hong Yan Wang, Lei Zhou, Kah Leong Lim, Eng-King Tan
Summary: This study found that the TH-DA pathway plays a critical role in the pathogenesis of Parkinson's disease. LRRK2 and PINK1 have opposing effects on the TH-DA pathway, and the balance between them affects the survival of DA neurons. Mutations in LRRK2 or PINK1 can disrupt this balance, leading to the demise of DA neurons.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Tohru Kitada, Mustafa T. Ardah, M. Emdadul Haque
Summary: Parkin, discovered 25 years ago as the gene responsible for hereditary Parkinson's disease, remains a subject of intense research interest. Despite extensive efforts, the function and mechanism of the Parkin protein in neuronal cell death and pathogenesis remain unknown. This review highlights the chronological research on the parkin gene and discusses unresolved issues, new trends in research, and the relationship between parkin and tumorigenesis from the perspective of Parkin's redox molecule.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Steven J. Lubbe, Bernabe Bustos, Jing Hu, Dimitri Krainc, Theresita Joseph, Jason Hehir, Manuela Tan, Weijia Zhang, Valentina Escott-Price, Nigel M. Williams, Cornelis Blauwendraat, Andrew B. Singleton, Huw R. Morris
Summary: Single PRKN mutations were found to be more common in PD patients than controls, with a >1.5-fold increased risk of PD. Carriers of these mutations tended to have a younger age at onset compared to non-carriers. There is preliminary evidence suggesting that carriers of single PRKN copy number variants may have a more pathogenic risk profile.
HUMAN MOLECULAR GENETICS
(2021)
Review
Biochemistry & Molecular Biology
Britney N. Lizama, Charleen T. Chu
Summary: Autophagy is crucial for cells to remove damaged components and is increasingly studied for its role in various diseases. Research on autophagy and mitochondrial quality control is expanding, particularly in relation to conditions like cancer, immune diseases, and neurodegenerative diseases.
MOLECULAR ASPECTS OF MEDICINE
(2021)
Review
Cell Biology
Maria Vizziello, Linda Borellini, Giulia Franco, Gianluca Ardolino
Summary: Mitochondrial dysfunction is considered a major pathway in Parkinson's disease, and studies on genetic forms have revealed the roles of PINK1 and Parkin in mitochondrial homeostasis. The PINK1/Parkin pathway mediates the process of mitophagy, which is crucial for maintaining mitochondrial health.
Review
Neurosciences
Iryna Kamienieva, Jerzy Duszynski, Joanna Szczepanowska
Summary: The familial form of Parkinson's disease is linked to mutations in specific genes, with mutations in the parkin gene being one of the most common causes of early-onset PD. Mitochondrial dysfunction is an emerging active player in the pathology of neurodegenerative diseases, as mitochondria are highly dynamic structures integrated with many cellular functions.
TRANSLATIONAL NEURODEGENERATION
(2021)
Article
Clinical Neurology
Jun-ying Li, Nan-nan Li, Ling Wang, Jia-xin Peng, Li-ren Duan, Chao-lan Chen, Rong Peng
Summary: This study reported a female from a Chinese family diagnosed with juvenile PD and treated with levodopa/benserazide throughout pregnancy. Results showed that the genetic testing of the patient was consistent with the PD phenotype and exhibited an autosomal recessive pattern. The patient's PD symptoms remained stable during pregnancy with levodopa/benserazide treatment.
JOURNAL OF NEUROLOGY
(2021)
Article
Clinical Neurology
Javier Jarazo, Kyriaki Barmpa, Jennifer Modamio, Claudia Saraiva, Sonia Sabate-Soler, Isabel Rosety, Anne Griesbeck, Florian Skwirblies, Gaia Zaffaroni, Lisa M. Smits, Jihui Su, Jonathan Arias-Fuenzalida, Jonas Walter, Gemma Gomez-Giro, Anna S. Monzel, Xiaobing Qing, Armelle Vitali, Gerald Cruciani, Ibrahim Boussaad, Francesco Brunelli, Christian Jager, Aleksandar Rakovic, Wen Li, Lin Yuan, Emanuel Berger, Giuseppe Arena, Silvia Bolognin, Ronny Schmidt, Christoph Schroeder, Paul M. A. Antony, Christine Klein, Rejko Kruger, Philip Seibler, Jens C. Schwamborn
Summary: This study investigated the differences between neurons derived from Parkinson's disease patients and controls, identifying potential pathways for targeted treatment. By correcting mutations and using a specific compound, improvements in metabolic properties and neuronal differentiation in patient-derived cells were observed. Treatment with a repurposed compound was shown to restore impaired dopaminergic differentiation in Parkinson's disease patient-derived cells.
MOVEMENT DISORDERS
(2022)
Review
Cell Biology
Elvira Pequeno Leites, Vanessa Alexandra Morais
Summary: Mitochondrial dysfunction, particularly related to the nuclear-encoded mitochondrial kinase PINK1, plays a crucial role in the development of Parkinson's disease. Recent discoveries suggest that disruptions in overall brain homeostasis may underlie the neurodegeneration seen in PD. The involvement of astrocytes and microglia lacking PINK1 in increased neuroinflammation and deficits in physiological roles highlight the importance of these cells in the pathophysiology of PD.
Article
Biochemistry & Molecular Biology
Anastasiia Bohush, Agnieszka Goral, Malgorzata Sierant, Barbara Nawrot, Wieslawa Lesniak, Anna Filipek
Summary: SGT1 protein is highly expressed in the mammalian brain, potentially involved in the pathogenesis of Parkinson's disease. Research has shown that SGT1 can protect cells from toxicity associated with Parkinson's disease inducers and influence the expression of related genes.
Article
Behavioral Sciences
Dicle Buyuktaskin, Elvan Iseri, Esra Guney, Zafer Gunendi, Bulent Cengiz
Summary: This study demonstrates impaired sensory processing in ASD evaluated by STD and its lack of relationship with subjective sensory symptoms and daily difficulties.
Review
Cell Biology
Collin M. Bantle, Warren D. Hirst, Andreas Weihofen, Evgeny Shlevkov
Summary: Mitochondrial dysfunction is a key feature of Parkinson's disease, impacting the functions of astrocytes in the brain. Important astrocytic functions rely on healthy mitochondria, presenting new challenges for therapeutic development.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Clinical Neurology
Sara Brunetti, Serena Micheletti, Ilaria Palmieri, Enza Maria Valente, Elisa Fazzi
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Clinical Neurology
Carlo Alberto Artusi, Elisa Montanaro, Roberto Erro, Nils Margraf, Christian Geroin, Andrea Pilotto, Luca Magistrelli, Francesca Spagnolo, Alberto Marchet, Lidia Sarro, Sofia Cuoco, Marta Sacchetti, Marianna Riello, Barbara Capellero, Paola Berchialla, Bettina Moeller, Beeke Vullriede, Maurizio Zibetti, Augusto Maria Rini, Paolo Barone, Cristoforo Comi, Alessandro Padovani, Michele Tinazzi, Leonardo Lopiano
Summary: Pisa syndrome and camptocormia in patients with Parkinson's disease are associated with neuropsychological functioning. Pisa syndrome patients showed worse visuospatial performances and subjective visual vertical perception, while camptocormia patients did not exhibit significant differences. Furthermore, more than 60% of patients with these postural abnormalities had reduced awareness of their condition.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2023)
Article
Clinical Neurology
Giovanna De Michele, Gianluigi Rosario Palmieri, Chiara Pane, Enza Maria Valente, Ilaria Palmieri, Carmen Diletta Paola Dello Iacovo, Nunzia Cuomo, Augusta Giglio, Natascia De Lucia, Tommasina Fico, Sandra Perillo, Giuseppe De Michele, Anna De Rosa
Summary: The aim of this study was to compare motor and non-motor symptoms between patients with GBA-related PD (GBA-PD) and idiopathic PD (iPD) using standardized and validated scales. The results showed that GBA-PD patients had a more severe and rapidly progressive disease, and more frequent positive family history for PD, akinetic-rigid phenotype, postural instability, dementia, and psychosis compared to iPD patients.
ACTA NEUROLOGICA BELGICA
(2023)
Article
Genetics & Heredity
Jessica Galli, Enza Maria Valente, Joseph Dewulf, Alessandra Franzoni, Sandrine Marie, Massimo Plumari, Federica Zanetti, Elisa Fazzi
Summary: 5-Amino-4-imidazolecarboxamide-ribosiduria (AICA-ribosiduria) is an extremely rare inborn error of purine biosynthesis metabolism. This study reports two new cases of AICA-ribosiduria with milder symptoms compared to previously reported patients. The study also found abnormal accumulation of purine biosynthesis intermediates in the urine of these patients.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Clinical Neurology
Davide Politano, Simone Gana, Elena Pezzotti, Angela Berardinelli, Ludovica Pasca, Veronica Carmen Barbero, Anna Pichiecchio, Enza Maria Valente, Edoardo Errichiello
Summary: Mutations in NEUROD2 gene may be associated with epilepsy and developmental delay. We report a case of a child with a novel NEUROD2 mutation, presenting with clinical features resembling Rett/Rett-like syndrome. Our findings suggest that NEUROD2 gene may play a crucial role in neurodevelopmental disorders.
BRAIN & DEVELOPMENT
(2023)
Article
Biochemistry & Molecular Biology
Paola Fortugno, Rosanna Monetta, Valeria Cinquina, Chiara Rigon, Francesca Boaretto, Chiara De Luca, Nicoletta Zoppi, Luana Di Leandro, Emanuela De Domenico, Arianna Di Daniele, Rodolfo Ippoliti, Francesco Angelucci, Ernesto Di Cesare, Ruggero De Paulis, Leonardo Salviati, Marina Colombi, Francesco Brancati, Marco Ritelli
Summary: Pathogenic variants in TGFBR1 are a common cause of Loeys-Dietz syndrome (LDS) characterized by life-threatening cardiovascular diseases. In this study, two novel variants in TGFBR1 were identified in LDS patients, resulting in truncated TGFBR1 proteins. These variants escaped nonsense-mediated mRNA decay and exhibited enhanced TGF beta signaling. The findings emphasize the importance of functional studies for accurate clinical diagnosis.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Correction
Cardiac & Cardiovascular Systems
Silvia Castelletti, Alessandro Zorzi, Enrico Ballardini, Cristina Basso, Alessandro Biffi, Francesco Brancati, Elena Cavarretta, Lia Crotti, Maurizio Contursi, Antonio D'Aleo, Flavio D'Ascenzi, Pietro Delise, Antonio Dello Russo, Giovanni Gazale, Lucio Mos, Valeria Novelli, Zefferino Palama, Stefano Palermi, Vincenzo Palmieri, Giampiero Patrizi, Antonio Pelliccia, Kalliopi Pilichou, Silvio Romano, Patrizio Sarto, Peter J. Schwartz, Monica Tiberi, Paolo Zeppilli, Domenico Corrado, Luigi Sciarra
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2023)
Article
Clinical Neurology
Eva-Juliane Vollstedt, Susen Schaake, Katja Lohmann, Shalini Padmanabhan, Alexis Brice, Suzanne Lesage, Christelle Tesson, Marie Vidailhet, Isabel Wurster, Faycel Hentati, Anat Mirelman, Nir Giladi, Karen Marder, Cheryl Waters, Stanley Fahn, Meike Kasten, Norbert Bruggemann, Max Borsche, Tatiana Foroud, Eduardo Tolosa, Alicia Garrido, Grazia Annesi, Monica Gagliardi, Maria Bozi, Leonidas Stefanis, Joaquim J. Ferreira, Leonor Correia Guedes, Micol Avenali, Simona Petrucci, Lorraine Clark, Ekaterina Y. Fedotova, Natalya Y. Abramycheva, Victoria Alvarez, Manuel Menendez-Gonzalez, Silvia Jesus Maestre, Pilar Gomez-Garre, Pablo Mir, Andrea Carmine Belin, Caroline Ran, Chin-Hsien Lin, Ming-Che Kuo, David Crosiers, Zbigniew K. Wszolek, Owen A. Ross, Joseph Jankovic, Kenya Nishioka, Manabu Funayama, Jordi Clarimon, Caroline H. Williams-Gray, Marta Camacho, Mario Cornejo-Olivas, Luis Torres-Ramirez, Yih-Ru Wu, Guey-Jen Lee-Chen, Ana Morgadinho, Teeratorn Pulkes, Pichet Termsarasab, Daniela Berg, Gregor Kuhlenbaumer, Andrea A. Kuhn, Friederike Borngraeber, Giuseppe de Michele, Anna De Rosa, Alexander Zimprich, Andreas Puschmann, George D. Mellick, Jolanta Dorszewska, Jonathan Carr, Rosangela Ferese, Stefano Gambardella, Bruce Chase, Katerina Markopoulou, Wataru Satake, Tatsushi Toda, Malco Rossi, Marcelo Merello, Timothy Lynch, Diana A. Olszewska, Shen-Yang Lim, Azlina Ahmad-Annuar, Ai Huey Tan, Bashayer Al-Mubarak, Hasmet Hanagasi, Dariusz Koziorowski, Sibel Ertan, Gencer Genc, Patricia de Carvalho Aguiar, Melinda Barkhuizen, Marcia M. G. Pimentel, Rachel Saunders-Pullman, Bart van de Warrenburg, Susan Bressman, Mathias Toft, Silke Appel-Cresswell, Anthony E. Lang, Matej Skorvanek, Agnita J. W. Boon, Rejko Kruger, Esther M. Sammler, Vitor Tumas, Bao-Rong Zhang, Gaetan Garraux, Sun Ju Chung, Yun Joong Kim, Juliane Winkelmann, Carolyn M. Sue, Eng-King Tan, Joana Damasio, Peter Klivenyi, Vladimir S. Kostic, David Arkadir, Mika Martikainen, Vanderci Borges, Jens Michael Hertz, Laura Brighina, Mariana Spitz, Oksana Suchowersky, Olaf Riess, Parimal Das, Brit Mollenhauer, Emilia M. Gatto, Maria Skaalum Petersen, Nobutaka Hattori, Ruey-Meei Wu, Sergey N. Illarioshkin, Enza Maria Valente, Jan O. Aasly, Anna Aasly, Roy N. Alcalay, Avner Thaler, Matthew J. Farrer, Kathrin Brockmann, Jean-Christophe Corvol, Christine Klein
Summary: Through a worldwide online survey, we established an international cohort of individuals with PD-linked variants, providing harmonized and quality-controlled clinical and genetic data for each participant and promoting collaboration among researchers in the field of monogenic PD.
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Mark A. Corbett, Christel Depienne, Liana Veneziano, Karl Martin Klein, Francesco Brancati, Renzo Guerrini, Federico Zara, Shoji Tsuji, Jozef Gecz
Summary: This review summarizes the history of genetic studies on Familial Adult Myoclonus Epilepsy (FAME) worldwide, covering the discovery of noncoding TTTTA and inserted TTTCA pentanucleotide repeat expansions within six different genes. FAME repeat expansions are dynamic in nature and have regional geographical distributions. Molecular diagnosis of FAME repeat expansions is challenging, requiring a trade-off between cost and efficiency. The discovery of FAME repeats will contribute to a better understanding of the molecular pathogenesis of FAME and the development of models for further research.
Review
Biochemistry & Molecular Biology
Malek Bouassida, Matthieu Egloff, Jonathan Levy, Nicolas Chatron, Laura Bernardini, Gwenael Le Guyader, Anne-Claude Tabet, Caroline Schluth-Bolard, Francesco Brancati, Maria Grazia Giuffrida, Rodolphe Dard, Juliette Clorennec, Juliette Coursimault, Francois Vialard, Berenice Herve
Summary: This study aimed to characterize the phenotypic spectrum of microduplications involving the MYT1L gene. Clinical features of patients with pure 2p25.3 microduplications were assessed, and the results showed variable phenotypes including developmental delays, autism spectrum disorders, intellectual disabilities, schizophrenia, and behavioral disorders. The study also revealed unknown genetic and nongenetic modifiers contributing to the incomplete penetrance and variable expressivity of these microduplications.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Valentina Serpieri, Giulia Mortarini, Hailey Loucks, Tommaso Biagini, Alessia Micalizzi, Ilaria Palmieri, Jennifer C. Dempsey, Fulvio D'Abrusco, Concetta Mazzotta, Roberta Battini, Enrico Silvio Bertini, Eugen Boltshauser, Renato Borgatti, Knut Brockmann, Stefano D'Arrigo, Nardo Nardocci, Rita Fischetto, Emanuele Agolini, Antonio Novelli, Alfonso Romano, Romina Romaniello, Franco Stanzial, Sabrina Signorini, Pietro Strisciuglio, Simone Gana, Tommaso Mazza, Dan Doherty, Enza Maria Valente
Summary: This study reports 11 recurring variants in Joubert syndrome patients, including three founder variants in specific populations. The variants were significantly enriched in the European Joubert syndrome cohort and showed different enrichments in American patients. Four new European founder haplotypes were also identified. Additionally, two variants were suggested to be hypomorphic variants.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Clinical Neurology
Pierre-Emmanuel Sugier, Elise A. Lucotte, Cloe Domenighetti, Matthew H. Law, Mark M. Iles, Kevin Brown, Christopher Amos, James D. McKay, Rayjean J. Hung, Mojgan Karimi, Delphine Bacq-Daian, Anne Boland-Auge, Robert Olaso, Jean-francois Deleuze, Fabienne Lesueur, Evgenia Ostroumova, Ausrele Kesminiene, Florent de Vathaire, Pascal Guenel, Ashwin Ashok Kumar Sreelatha, Claudia Schulte, Sandeep Grover, Patrick May, Dheeraj R. Bobbili, Milena Radivojkov-Blagojevic, Peter Lichtner, Andrew B. Singleton, Dena G. Hernandez, Connor Edsall, George D. Mellick, Alexander Zimprich, Walter Pirker, Ekaterina Rogaeva, Anthony E. Lang, Sulev Koks, Pille Taba, Suzanne Lesage, Alexis Brice, Jean-Christophe Corvol, Marie-Christine Chartier-Harlin, Eugenie Mutez, Kathrin Brockmann, Angela B. Deutschlaender, Georges M. Hadjigeorgiou, Efthimios Dardiotis, Leonidas Stefanis, Athina Maria Simitsi, Enza Maria Valente, Simona Petrucci, Letizia Straniero, Anna Zecchinelli, Gianni Pezzoli, Laura Brighina, Carlo Ferrarese, Grazia Annesi, Andrea Quattrone, Monica Gagliardi, Hirotaka Matsuo, Akiyoshi Nakayama, Nobutaka Hattori, Kenya Nishioka, Sun Ju Chung, Yun Joong Kim, Pierre Kolber, Bart P. C. van de Warrenburg, Bastiaan R. Bloem, Jan Aasly, Mathias Toft, Lasse Pihlstrom, Leonor Correia Guedes, Joaquim J. Ferreira, Soraya Bardien, Jonathan Carr, Eduardo Tolosa, Mario Ezquerra, Pau Pastor, Monica Diez-Fairen, Karin Wirdefeldt, Nancy Pedersen, Caroline Ran, Andrea C. Belin, Andreas Puschmann, Emil Ygland Roedstroem, Carl E. Clarke, Karen E. Morrison, Manuela Tan, Dimitri Krainc, Lena F. Burbulla, Matt J. Farrer, Rejko Kruger, Thomas Gasser, Manu Sharma, Therese Truong, Alexis Elbaz
Summary: By using genome-wide association studies, this study found that Parkinson's disease (PD) is genetically correlated with melanoma and prostate cancer, while it is inversely correlated with ovarian cancer. These findings suggest that pleiotropic genes contribute to the association between PD and specific cancers.
MOVEMENT DISORDERS
(2023)
Letter
Clinical Neurology
Marco Percetti, Edoardo Monfrini, Leonardo Caporali, Raffaella Minardi, Valerio Carelli, Enza Maria Valente, Alessio Di Fonzo
MOVEMENT DISORDERS
(2023)
Article
Genetics & Heredity
Simone Schroeder, Goekhan Yigit, Yun Li, Janine Altmueller, Hans-Martin Buettel, Barbara Fiedler, Christoph Kretzschmar, Peter Nuernberg, Juergen Seeger, Valentina Serpieri, Enza Maria Valente, Bernd Wollnik, Eugen Boltshauser, Knut Brockmann
Summary: Congenital ocular motor apraxia (COMA) is a heterogeneous eye movement disorder with various underlying genetic causes. In this study, researchers re-evaluated the neuroimaging features of 21 patients with COMA and discovered a novel sign, molar tooth sign (MTS), leading to a reassignment of diagnosis to Joubert syndrome (JBTS) in some patients. Using genetic analysis, pathogenic variants were identified in 81% of the patients, involving nine different genes. A diagnostic algorithm for COMA was proposed based on these findings.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Editorial Material
Clinical Neurology
Roberto Erro, Marina Picillo, Maria Teresa Pellecchia, Paolo Barone
JOURNAL OF MOVEMENT DISORDERS
(2023)