Article
Clinical Neurology
Francesca Magrinelli, Elisa Cali, Vinicius Lopes Braga, Uluc Yis, Hoda Tomoum, Hanan Shamseldin, Julian Raiman, Christoph Kernstock, Flavio Moura Rezende Filho, Orlando Graziani Povoas Barsottini, Robert W. Taylor, Elsebet Ostergaard, Abdullah Tamim, Karin Schaeferhoff, Juliana Maria Ferraz Sallum, Maha S. Zaki, Fernando Kok, Kailash P. Bhatia, Bernd Wissinger, Kate Sergeant, Tobias B. Haack, Rita Horvath, Semra Hiz, Fowzan S. Alkuraya, Henry Houlden, Jose Luiz Pedroso, Reza Maroofian
Summary: This study presents newly identified cases of NDUFA12-related mitochondrial disease, demonstrating phenotypic and genotypic heterogeneity. The cases exhibited various clinical presentations, including movement disorders and optic atrophy, with distinct MRI findings. The study highlights the clinical diversity associated with the same genetic variant within and between families.
MOVEMENT DISORDERS CLINICAL PRACTICE
(2022)
Article
Clinical Neurology
Sarah L. Stenton, Marketa Tesarova, Natalia L. Sheremet, Claudia Catarino, Valerio Carelli, Elzbieta Ciara, Kathryn Curry, Martin Engvall, Leah R. Fleming, Peter Freisinger, Katarzyna Iwanicka-Pronicka, Elzbieta Jurkiewicz, Thomas Klopstock, Mary K. Koenig, Hana Kolarova, Bohdan Kousal, Tatiana Krylova, Chiara La Morgia, Lenka Noskova, Dorota Piekutowska-Abramczuk, Sam N. Russo, Viktor Stranecky, Iveta Tothova, Frank Traisk, Holger Prokisch
Summary: The study identified 28 previously unreported individuals carrying the DNAJC30 variant, expanding the spectrum of Leber hereditary optic neuropathy and Leigh syndrome. The findings confirmed sex-dependent incomplete penetrance of the homozygous variant and the association of DNAJC30 with Leigh syndrome.
Article
Health Care Sciences & Services
Qifei Li, Jill A. Madden, Jasmine Lin, Jiahai Shi, Samantha M. Rosen, Klaus Schmitz-Abe, Pankaj B. Agrawal
Summary: Mutations in SLC25A46 have been associated with various neurological diseases, and two novel variants were identified in a patient with neurological phenotype. These variants may play a causative role in the observed neurological symptoms.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Juliane Muench, Jannik Prasuhn, Lucia Laugwitz, Cheuk-Wing Fung, Brian H. -Y. Chung, Marcello Bellusci, Ertan Mayatepek, Dirk Klee, Felix Distelmaier
Summary: CoQ(10) is a lipid molecule synthesized within the body, known for its role in the mitochondrial respiratory chain and various cellular pathways. Mutations in CoQ(10) biosynthesis enzymes have been identified, leading to variable disease onset and detrimental effects on the nervous system. Brain MRI is crucial for diagnosing neurological damage in CoQ(10) deficiency, but information on disease manifestations is scarce due to the rarity of gene defects. This review provides an overview of brain MRI patterns and disease-specific findings in primary CoQ(10) biosynthesis disorders.
Article
Genetics & Heredity
Marta Zawadzka, Magdalena Krygier, Malgorzata Pawlowicz, Matheus Vernet Machado Bressan Wilke, Karolina Rutkowska, Naig Gueguen, Valerie Desquiret-Dumas, Eric W. Klee, Lisa A. Schimmenti, Jaroslaw Slawek, Vincent Procaccio, Rafal Ploski, Maria Mazurkiewicz-Beldzinska
Summary: Leigh syndrome is a progressive neurodegenerative disease with extensive clinical and biochemical features. This study describes three Polish patients and provides further evidence for the association of DNAJC30 gene variants with Leigh syndrome. DNAJC30-associated Leigh syndrome exhibits clinical heterogeneity with variable age at onset, movement disorder phenotype, and blood lactate level.
Article
Clinical Neurology
Thiago Cardoso Vale, Orlando Graziani Povoas Barsottini, Jose Luiz Pedroso
Summary: A 30-year-old man presented with a two-year history of involuntary movements in the face and mouth, showing isolated orofacial dystonia on neurological examination. He was born from non-consanguineous parents, had normal development, and did not have any other neurological abnormalities.
PARKINSONISM & RELATED DISORDERS
(2021)
Article
Biochemistry & Molecular Biology
Romina Romaniello, Ludovica Pasca, Elena Panzeri, Fulvio D'Abrusco, Lorena Travaglini, Valentina Serpieri, Sabrina Signorini, Chiara Aiello, Enrico Bertini, Maria Teresa Bassi, Enza Maria Valente, Ginevra Zanni, Renato Borgatti, Filippo Arrigoni
Summary: Pathogenic variants in the ITPR1 gene are associated with autosomal dominant spinocerebellar ataxia. Superior vermian and hemispheric cerebellar atrophy on MRI can be a distinguishing feature of ITPR1-related disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Ophthalmology
Alexander M. Warwick, Howard M. Bomze, Luyu Wang, Mikael Klingeborn, Ying Hao, Sandra S. Stinnett, Sidney M. Gospe
Summary: Continuous hypoxia was found to have a significant neuroprotective effect on early retinal ganglion cell degeneration in mice with severe mitochondrial dysfunction. However, the complete rescue effect was not durable after a certain period of time. Hypoxia prevented gliosis but had limited effect on the accumulation of mononuclear phagocytic cells.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Genetics & Heredity
Yuri Seo, Hyun Taek Lim, Byung Joo Lee, Jinu Han
Summary: This study reported a 15-year-old male patient who displayed isolated optic atrophy and infantile nystagmus before the onset of neurological symptoms. A novel heterozygous variant in the SPG7 gene was found to be the cause. Therefore, SPG7 should be considered as a potential cause for infantile nystagmus with optic atrophy.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Review
Clinical Neurology
Melissa A. E. van de Wal, Merel J. W. Adjobo-Hermans, Jaap Keijer, Tom J. J. Schirris, Judith R. Homberg, Mariusz R. Wieckowski, Sander Grefte, Evert M. van Schothorst, Clara van Karnebeek, Albert Quintana, Werner J. H. Koopman
Summary: Mitochondrial dysfunction is associated with various syndromes and diseases, including Leigh syndrome. Mutations in the NDUFS4 gene can cause Leigh syndrome, and studying it in mouse models has provided new insights into the pathomechanism and treatment.
Article
Genetics & Heredity
Joana Damasio, Mariana Santos, Raquel Samoes, Maria Araujo, Mafalda Macedo, Ana Sardoeira, Sara Cavaco, Joel Freitas, Jose Barros, Jorge Oliveira, Jorge Sequeiros
Summary: Hereditary cerebellar ataxias are a group of neurodegenerative disorders affecting the cerebellum and/or cerebellar pathways. Next-generation sequencing has expanded the understanding of genes causing ataxia. The study suggests KMT2B may be involved in hereditary cerebellar ataxias.
Article
Endocrinology & Metabolism
Laura Marti-Sanchez, Heidy Baide-Mairena, Anna Marce-Grau, Roser Pons, Anastasia Skouma, Eduardo Lopez-Laso, Maria Sigatullina, Cristiano Rizzo, Michela Semeraro, Diego Martinelli, Rosalba Carrozzo, Carlo Dionisi-Vici, Luis Gonzalez-Gutierrez-Solana, Marta Correa-Vela, Juan Dario Ortigoza-Escobar, Angel Sanchez-Montanez, Elida Vazquez, Ignacio Delgado, Sergio Aguilera-Albesa, Maria Eugenia Yoldi, Antonia Ribes, Frederic Tort, Luca Pollini, Serena Galosi, Vincenzo Leuzzi, Manuela Tolve, Laura Perez-Gay, Luis Aldamiz-Echevarria, Mireia Del Toro, Antonio Arranz, Filip Roelens, Roser Urreizti, Rafael Artuch, Alfons Macaya, Belen Perez-Duenas
Summary: The neurological phenotype of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) and short-chain enoyl-CoA hydratase (SCEH) defects is expanding, and natural history studies are needed for better clinical management. Through genetic analysis, it was found that HIBCH patients tend to have longer survival compared to SCEH patients. Various novel pathogenic variants were identified, providing valuable information for predicting outcomes and enhancing clinical care.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Clinical Neurology
Sophia Caldas Gonzaga da Costa, Flavio e de Rezende-Filho, Julian Leticia de Freitas, Paula Camila Alves de Assis Pereira Matos, Bruno Della-Ripa, Marcondes Cavalcante Franca, Wilson Marques, Mariana Santos, Igor Vasconcelos Barros Cronemberger, Thiago Cardoso Vale, Fernando Kok, Isabel Alonso, Jose Luiz Pedroso, Orlando G. P. Barsottini
Summary: Through genetic investigation, it was found that AOA2 and AOA4 were the most common subtypes of autosomal recessive cerebellar ataxia plus oculomotor apraxia in Brazil. Pathogenic variants in SETX, PNKP, and APTX genes were frequently identified, while mutations in PIK3R5 and XRCC1 were less common.
MOVEMENT DISORDERS
(2022)
Article
Clinical Neurology
Matej Skorvanek, Robert Jech, Juliane Winkelmann, Michael Zech
Summary: A male patient with immunodeficiency of unknown etiology since childhood developed a medication-refractory choreodystonic movement disorder at the age of 42. Exome-wide molecular testing revealed a pathogenic variant in the CD40LG gene, confirming the existence of a CD40LG-related condition combining compromised immunity with neurodegenerative movement abnormalities. Establishing the diagnosis is crucial due to potential life-threatening immunological complications.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Clinical Neurology
Shuang Wang, Jing Miao, Jiachun Feng
Summary: This case highlights the clinical manifestations of multi-system mitochondrial disease in a male patient, including neurological impairment without myopathy. Diagnosis was confirmed through muscle biopsy and mtDNA testing, leading to effective treatment with anti-epileptic drugs and mitochondrial supplements.
FRONTIERS IN NEUROLOGY
(2021)
Article
Genetics & Heredity
Nitzan Vigdorovich, Liat Ben-Sira, Lubov Blumkin, Ronit Precel, Ifat Nezer, Keren Yosovich, Zachary Cross, Adeline Vanderver, Dorit Lev, Tally Lerman-Sagie, Ayelet Zerem
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2020)
Article
Genetics & Heredity
Michal Gafner, Marina Michelson, Keren Yosovich, Lubov Blumkin, Tally Lerman-Sagie, Dorit Lev
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2020)
Article
Clinical Neurology
Lubov Blumkin, Zvi Leibovitz, Karina Krajden-Haratz, Ayala Arad, Keren Yosovich, Liat Gindes, Ayelet Zerem, Liat Ben-Sira, Dorit Lev, Andrea Nissenkorn, Dvora Kidron, William B. Dobyns, Gustavo Malinger, Nadia Bahi-Buisson, Richard J. Leventer, Tally Lerman-Sagie
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2020)
Article
Genetics & Heredity
Tamar Borkowski, Raquel Garcia-Rodriguez, Fernando Vinals, Miguel Branco, Karina Kradjen-Haratz, Liat Ben-Sira, Tally Lerman-Sagie, Gustavo Malinger
PRENATAL DIAGNOSIS
(2020)
Article
Genetics & Heredity
Tamar Gur Hartman, Keren Yosovich, Hila Gur Michaeli, Lubov Blumkin, Liat Ben-Sira, Dorit Lev, Tally Lerman-Sagie, Ayelet Zerem
Article
Genetics & Heredity
Michal Levy, Dorit Lev, Zvi Leibovitz, Alon Kashanian, Liat Gindes, Mordechai Tamarkin, Josef Shalev, Liat B. Sira, Yossi Mizrachi, Adi Borovich, Roee Birnbaum, Tally Lerman-Sagie, Gustavo Malinger, Karina K. Haratz
PRENATAL DIAGNOSIS
(2020)
Article
Genetics & Heredity
Michal M. Andelman-Gur, Richard J. Leventer, Mohammad Hujirat, Christos Ganos, Keren Yosovich, Nirit Carmi, Dorit Lev, Andreea Nissenkorn, William B. Dobyns, Kailash Bhatia, Tally Lerman-Sagie, Lubov Blumkin
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2020)
Article
Clinical Neurology
Tamar Gur-Hartman, Oren Berkowitz, Keren Yosovich, Agathe Roubertie, Ginevra Zanni, Alfons Macaya, Gali Heimer, Belen Perez Duenas, Deborah A. Sival, Ben Pode-Shakked, Eduardo Lopez-Laso, Veronique Humbertclaude, Florence Riant, Luca Bosco, Lital Bachar Cayron, Andreea Nissenkorn, Francesco Nicita, Enrico Bertini, Sharon Hassin, Bruria Ben Zeev, Ayelet Zerem, Stephanie Libzon, Dorit Lev, Ilan Linder, Tally Lerman-Sagie, Lubov Blumkin
Summary: The study revealed that the phenotypes in infantile-onset CACNA1A-related disorders mainly include cerebellar ataxia and paroxysmal non-epileptic events, with overlap in the majority of patients. Some patients may develop epilepsy in later childhood.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2021)
Article
Genetics & Heredity
Michal M. Andelman-Gur, Hirotomo Saitsu, Naomichi Matsumoto, Ronen Spiegel, Keren Yosovich, Dorit Lev, Tally Lerman-Sagie, Lubov Blumkin
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2020)
Article
Clinical Neurology
Andreea Nissenkorn, Keren Yosovich, Zvi Leibovitz, Tamar Gur Hartman, Itay Zelcer, Mohammad Hugirat, Dorit Lev, Tally Lerman-Sagie, Lubov Blumkin
Summary: Congenital mirror movements are involuntary movements that mimic intentional movements on the opposite side, often persisting beyond 7 years of age. These movements are usually idiopathic but can be associated with various brain malformations. This study describes the clinical, genetic, and radiologic features in individuals with congenital mirror movements, and identifies specific genetic mutations in DCC, TUBB3, TUBB, TUBA1A, and POMGNT1 that are linked to abnormal axonal guidance and brain malformations.
JOURNAL OF CHILD NEUROLOGY
(2021)
Article
Endocrinology & Metabolism
Orna Staretz-Chacham, Suha Daas, Igor Ulanovsky, Ayala Blau, Nira Rostami, Talya Saraf-Levy, Nasser Abu Salah, Yair Anikster, Ehud Banne, Dalit Dar, Elena Dumin, Aviva Fattal-Valevski, Tzipora Falik-Zaccai, Eli Hershkovitz, Sagi Josefsberg, Hatem Khammash, Rimona Keidar, Stanley H. Korman, Yuval Landau, Tally Lerman-Sagie, Dror Mandel, Hanna Mandel, Ronella Marom, Iris Morag, Erez Nadir, Naama Yosha-Orpaz, Ben Pode-Shakked, Elon Pras, Haike Reznik-Wolf, Ann Saada, Reeval Segel, Avraham Shaag, Nava Shaul Lotan, Ronen Spiegel, Galit Tal, Taly Vaisid, Avi Zeharia, Shlomo Almashanu
Summary: Urea cycle disorders, including OTCD, are serious diseases with a wide range of clinical manifestations. Utilizing a new method of screening for OTCD based on the combined measurement of orotic acid and citrulline may improve the early detection of UCDs and differentiate between different types of disorders.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Clinical Neurology
Aviva Fattal-Valevski, Liat Ben Sira, Tally Lerman-Sagie, Rachel Strausberg, Aviva Bloch-Mimouni, Simon Edvardson, Rami Kaufman, Veronika Chernuha, Nira Schneebaum Sender, Gali Heimer, Bruria Ben Zeev
Summary: The study examined patients with a homozygous founder mutation c.1112T>C in MED17 gene, leading to postnatal progressive microcephaly. Patients showed a unique clinical phenotype with severe intellectual disability, epilepsy, and progressive spasticity. MRI findings revealed marked cerebral and cerebellar atrophy in these patients.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2021)
Article
Endocrinology & Metabolism
Ayelet Zerem, Liat Ben-Sira, Nitzan Vigdorovich, Zvi Leibovitz, Yael Fisher, Raphael Schiffmann, Yulia Grishchuk, Albert L. Misko, Naama Orenstein, Dorit Lev, Tally Lerman-Sagie, Debora Kidron
Summary: This study describes novel fetal brain MRI and neuropathology findings in a fetus with Mucolipidosis type IV, showing prenatal white matter involvement, significant activation of microglia and astrocytes, and impaired iron metabolism.
METABOLIC BRAIN DISEASE
(2021)
Article
Genetics & Heredity
Michal Gafner, Marina Michelson, Emanuela Argilli, Keren Yosovich, Elliott H. Sherr, Kendall C. Parks, Eleina M. England, Ronen Hady-Cohen, Zvi Leibovitz, Dorit Lev, Yael Michaeli-Yosef, Tally Lerman-Sagie, Lubov Blumkin
Summary: Through case reports from two unrelated families, it was revealed that BCORL1 gene mutations may lead to major brain developmental abnormalities including hypoplastic corpus callosum, septal agenesis, and unilateral perisylvian polymicrogyria. The mothers of these patients were carriers of the mutated gene, indicating a potential influence of BCORL1 on brain development.
JOURNAL OF HUMAN GENETICS
(2022)
Article
Pediatrics
Revital Ben-Haim, Eli Heyman, Lilach Benyamini, Daniel Shapira, Dorit Lev, Michal Tzadok, Tally Lerman-Sagie, Hirotomo Saitsu, Naomichi Matsumoto, Kazuhiro Iwama, Mirit Lazinger, Haim Bassan
JOURNAL OF PEDIATRIC NEUROLOGY
(2020)