Article
Genetics & Heredity
Juan L. Garcia-Hernandez, Luis A. Corchete, Inigo Marcos-Alcalde, Paulino Gomez-Puertas, Carmen Fons, Pedro A. Lazo
Summary: Complex developmental encephalopathy syndromes may result from unknown genetic alterations that impact the neurological phenotype through pathogenic gene combinations. A study of a patient with a KCNQ2 gene mutation revealed severe neurological issues potentially linked to multiple gene mutations and brain function.
Article
Genetics & Heredity
Chawan Manaspon, Ponghatai Boonsimma, Chureerat Phokaew, Thanakorn Theerapanon, Kanokwan Sriwattanapong, Thantrira Porntaveetus, Vorasuk Shotelersuk
Summary: PYCR2 pathogenic variants cause HLD10 in two unrelated Thai patients, with patient 1 having compound heterozygous variants and patient 2 having a homozygous variant. Haplotype analysis revealed a common ancestry dating back to approximately 1450 years ago for the identified variant. Majority of previously reported PYCR2 patients were homozygous with consanguineous family history, except for a few compound heterozygous cases.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Article
Multidisciplinary Sciences
Tingting Jin, Ying Kuang, Shulin Luo, Rongpin Wang, Kun Chen, Minmin Jiang, Lingyan Ren, Zhaolin Sun, Lifen Duan, Shengwen Huang
Summary: This study describes a child with microcephaly and recurrent seizures. Whole-exome sequencing identified two novel compound heterozygous mutations in the AFG3L2 gene, expanding the mutation spectrum and identifying a severe neurodegenerative phenotype of global cerebral atrophy caused by biallelic AFG3L2 mutations.
Review
Genetics & Heredity
Lavinia Schuler-Faccini, Miguel del Campo, Alfredo Garcia-Alix, Liana O. Ventura, Juliano Andre Boquett, Vanessa van der Linden, Andre Pessoa, Helio van der Linden Junior, Camila V. Ventura, Mariana Carvalho Leal, Thayne Woycinck Kowalski, Lais Rodrigues Gerzson, Carla Skilhan de Almeida, Lucelia Santi, Walter O. Beys-da-Silva, Andre Quincozes-Santos, Jorge A. Guimaraes, Patricia P. Garcez, Julia do Amaral Gomes, Fernanda Sales Luiz Vianna, Andre Anjos da Silva, Lucas Rosa Fraga, Maria Teresa Vieira Sanseverino, Alysson R. Muotri, Rafael Lopes da Rosa, Alberto Mantovani Abeche, Clairton Marcolongo-Pereira, Diogo O. Souza
Summary: This article reviews the identification of Zika virus as a human teratogen and its effects on congenital Zika syndrome (CZS). This syndrome is characterized by severe motor, cognitive, and language impairments, particularly in the form of cerebral palsy. However, some children may exhibit milder deficits, and those born without brain or eye abnormalities can have normal neurodevelopment. Vertical transmission and disruption in brain development are less frequent when maternal infection occurs in the second half of pregnancy. Experimental studies indicate the possibility of other behavioral outcomes in prenatally infected children, as well as in postnatal and adult infections. The development of CZS is influenced by various factors, including genetics, environment, nutrition, and social determinants.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Ali Reza Tavasoli, Elmira Haji Esmaeil Memar, Mahmoud Reza Ashrafi, Seyed Mohammad Mahdi Hosseini, Roya Haghighi, Homa Ghabeli, Elham Pourbakhtyaran, Maryam Rasoulinezhad, Pouria Mohammadi, Morteza Heidari
Summary: This study describes two siblings with microcephaly, one with primary microcephaly and one with secondary microcephaly, who both have the same genetic variant in the ZNF335 gene. Whole-exome sequencing and segregation analysis confirmed the variant and predicted its damaging effect.
JOURNAL OF MOLECULAR NEUROSCIENCE
(2022)
Article
Genetics & Heredity
Viraj Patel, Wei Cui, Jan M. Cobben
Summary: We present a case of a boy with SHORT syndrome characterized by microcephaly and severe developmental delay caused by a de novo PIK3R1 gene variant. Our findings coincide with a similar case from Brazil and other reported cases, all of which have variants in the iSH2 domain of the PIK3R1 gene. These findings suggest that iSH2 domain variants in PIK3R1 may be associated with a distinct clinical presentation of SHORT syndrome characterized by microcephaly and intellectual/developmental disabilities. The underlying pathogenic mechanism of this association remains unknown.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Review
Neurosciences
Abraham Andreu-Cervera, Martin Catala, Sylvie Schneider-Maunoury
Summary: Development of the forebrain heavily relies on the Sonic Hedgehog (Shh) signaling pathway and functional primary cilia. Dysfunction of cilia may lead to ciliopathies, affecting multiple organs and potentially causing forebrain malformations. Therefore, further research is needed to investigate the relationship between forebrain defects in ciliopathies and the disruption of the Shh pathway.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Medicine, General & Internal
Preeti Srivastava, Asit Kumar Mishra, Nilanjan Sarkar
Summary: Hypomyelinating leukodystrophy is a genetically heterogeneous group of diseases affecting the central nervous system, resulting in improper formation of myelin sheaths. Clinical presentations include motor dysfunction and cognitive and language impairment, with genetic testing playing a key role in diagnosis.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2021)
Article
Endocrinology & Metabolism
Sara M. Fielder, Jill A. Rosenfeld, Lindsay C. Burrage, Lisa Emrick, Seema Lalani, Ruben Attali, Joshua N. Bembenek, Hieu Hoang, Dustin Baldridge, Gary A. Silverman, Tim Schedl, Stephen C. Pak
Summary: The study identified a damaging variant in the PPP5C gene, which has not been associated with Mendelian diseases previously. Functional evaluation in C. elegans showed that the variant is likely a strong hypomorph or complete loss-of-function.
MOLECULAR GENETICS AND METABOLISM
(2022)
Review
Clinical Neurology
Alejandra Vasquez, Ersida Buraniqi, Elaine C. Wirrell
Summary: This review summarizes the treatments for Developmental and Epileptic Encephalopathies (DEEs), with a focus on new and emerging pharmacologic therapies. Recent advances in molecular genetics and neurobiology have identified underlying pathophysiologic mechanisms involved in DEEs, which can be targeted with precision therapies or repurposed drugs. Some of these therapies are currently in clinical trials. The development of these new therapies has the potential to improve seizure burden and neurological outcomes in DEEs patients.
CURRENT OPINION IN NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ana Ching-Lopez, Luis Javier Martinez-Gonzalez, Luisa Arrabal, Jorge Saiz, Angela Gavilan, Coral Barbas, Jose Antonio Lorente, Susana Roldan, Maria Jose Sanchez, Purificacion Gutierrez-Rios
Summary: The successful genetic diagnosis of infantile chronic progressive cerebellar ataxia revealed the association between POLR1C gene mutations and hypomyelinating leukodystrophy, highlighting the importance of multi-omics approaches in disease research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Zia Ur Rehman
Summary: This study investigated the clinical characteristics and etiology of epilepsy in children below two years of age. The findings showed that generalized seizures were the most common type, and structural abnormalities were the most common cause of epilepsy in these children. The age range of one to two years was identified as the most common onset period for seizures in young children.
CUREUS JOURNAL OF MEDICAL SCIENCE
(2022)
Article
Clinical Neurology
Shinobu Fukumura, Takuya Hiraide, Akiyo Yamamoto, Kousuke Tsuchida, Kazushi Aoto, Mitsuko Nakashima, Hirotomo Saitsu
Summary: This case report describes a 5-year-old girl with severe global developmental delay and hypomyelination caused by a novel de novo TMEM63A variant. The findings suggest that TMEM63A-related clinical spectrum is broad and can include severe developmental delay and seizures.
BRAIN & DEVELOPMENT
(2022)
Article
Genetics & Heredity
Haiming Yuan, Shaofang Shangguan, Zhengchang Li, Jingsi Luo, Jiasun Su, Ruen Yao, Shun Zhang, Chen Liang, Qian Chen, Zhijie Gao, Yanli Zhu, Shujie Zhang, Wei Li, Weiliang Lu, Yu Zhang, Hua Xie, Fang Liu, Qingming Wang, Yangyang Lin, Liying Liu, Xiuming Wang, Liyang Liang, Jianmin Zhong, Haibo Li, Haiyan Qiu, Huifeng Zhang, Mei Yan, Maimaiti Mireguli, Yanhui Liu, Dan Zhang, Hongying Wang, Haitao Lv, Bobo Xie, Chunrong Gui, Xiaodai Cui, Liping Zou, Jian Wang, James F. Gusella, Yiping Shen, Xiaoli Chen
Summary: The study aimed to analyze the CNV landscape in Chinese pediatric patients with developmental disorders. The results showed that there were differences in CNV frequencies and phenotypic diversity between Chinese and Western patients. The study highlighted the importance of understanding genetic variations in different populations for precision medicine.
GENETICS IN MEDICINE
(2021)
Article
Multidisciplinary Sciences
Anna Katharina Schlusche, Sabine Ulrike Vay, Niklas Kleinenkuhnen, Steffi Sandke, Rafael Campos-Martin, Marta Florio, Wieland Huttner, Achim Tresch, Jochen Roeper, Maria Adele Rueger, Igor Jakovcevski, Malte Stockebrand, Dirk Isbrandt
Summary: The development of the cerebral cortex relies on the controlled division of neural stem and progenitor cells, with ion channels playing a crucial role in shaping the intrinsic properties of precursor cells and neurons. Dysfunction in HCN channels can impair proliferation and cause microcephaly in rodents, highlighting the importance of ion channels in cortical development in mammals.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Clinical Neurology
Ana Filipa Geraldo, Cesar Augusto P. F. Alves, Aysha Luis, Domenico Tortora, Joana Guimaraes, Daisy Abreu, Sofia Reimao, Marco Pavanello, Patrizia de Marco, Marcello Scala, Valeria Capra, Rui Vaz, Andrea Rossi, Erin Simon Schwartz, Kshitij Mankad, Mariasavina Severino
Summary: This study investigates the neuroimaging findings and longitudinal evaluation of familial cerebral cavernous malformations (FCCM) in children. It reveals that the incidence and risk factors of symptomatic hemorrhage in children with FCCM are comparable to those in adults. Imaging features at the first brain MRI may help predict future symptomatic hemorrhage.
Review
Pediatrics
Andrea Rossi, Maria Argyropoulou, Dora Zlatareva, Gregoire Boulouis, Francesca B. Pizzini, Luc van den Hauwe, Maria Raissaki, Jean-Pierre Pruvo, Karen Rosendahl, Chen Hoffmann, Pia C. Sundgren
Summary: This article discusses the importance of pediatric neuroradiology and the lack of standardized training programs in European countries. It provides recommendations and guidance for the safe practice of pediatric neuroradiology, including imaging techniques, facility requirements, and team requirements.
PEDIATRIC RADIOLOGY
(2023)
Review
Pediatrics
Clara Adriana Maria de Bruijn, Stefano Di Michele, Maria Luisa Tataranno, Luca Antonio Ramenghi, Andrea Rossi, Mariya Malova, Manon Benders, Agnes van den Hoogen, Jeroen Dudink
Summary: This study evaluated the influence of punctate white matter lesions (PWML) on long-term neurodevelopmental outcomes in preterm infants. The findings showed a correlation between PWML and motor delay, as well as between PWML and cognitive and behavioral outcomes. The severity and types of impairments were found to be related to the number and location of PWML.
PEDIATRIC RESEARCH
(2023)
Article
Clinical Neurology
Vincenzo Daniele Boccia, Caterina Lapucci, Maria Cellerino, Francesco Tazza, Andrea Rossi, Simona Schiavi, Maria Margherita Mancardi, Matilde Inglese
Summary: The contribution of the central vein sign (CVS) to the diagnosis of multiple sclerosis (MS) was compared between pediatric-onset (POMS) and adult-onset (AOMS) patients. The study found that CVS had lower sensitivity in POMS patients, possibly due to the exclusion of a high proportion of periventricular confluent lesions from CVS assessment.
MULTIPLE SCLEROSIS JOURNAL
(2023)
Article
Clinical Neurology
Silvia Boeri, Marina Martinez Popple, Thea Giacomini, Tommaso Bellini, Mariasavina Severino, Andrea Rossi, Carla Debbia, Silvana Ancona, Elena Aldera, Lino Nobili, Laura Siri
Summary: A 12-year-old boy developed central nervous system demyelinating lesions following SARS-CoV-2 infection. He experienced symptoms such as headache and orbital pain, but recovered well after treatment. This case contributes to expanding our understanding of possible complications of COVID-19 and serves as a reminder not to overlook mild neurological symptoms associated with the disease.
Article
Clinical Neurology
Gelsomina Aruta, Pietro Fiaschi, Marco Ceraudo, Gianluca Piatelli, Valeria Capra, Andrea Bianconi, Andrea Rossi, Francesca Secci, Marco Pavanello
Summary: This article examines the association between multisutural craniosynostosis with Chiari malformation (CM), venous hypertension, and hydrocephalus, and proposes a simple and effective therapeutic flow-chart for managing these rare pathologies.
PEDIATRIC NEUROSURGERY
(2023)
Article
Pediatrics
Khalid Taha, Atul Sharma, Kristine Kroeker, Colin Ross, Bruce Carleton, David Wishart, Mara Medeiros, Tom D. D. Blydt-Hansen
Summary: This study aims to develop a novel urine test based on metabolomics to estimate the exposure of mycophenolate in pediatric renal transplantation. The urine samples were analyzed for 133 unique metabolites, and a top 10 urinary metabolite classifier was developed to estimate MPA exposure. The test was validated and showed correlation with allograft inflammation and eGFR ratio.
PEDIATRIC TRANSPLANTATION
(2023)
Review
Genetics & Heredity
Li Shu, Tatiana Maroilley, Maja Tarailo-Graovac
Summary: Complex genetic disease mechanisms, such as structural or non-coding variants, pose challenges in frontline diagnostic tests. Clinical diagnosis can help narrow down the genetic focus for patients with well-defined syndromes, allowing deeper analysis of complex genetic origins. Clinical-diagnosis-driven genome sequencing strategies can expedite the development of testing and analytical methods, advancing understanding and management of complex disease mechanisms.
Article
Clinical Neurology
Tatiana Maroilley, Meng-Han Tsai, Rumika Mascarenhas, Catherine Diao, Maryam Khanbabaei, Sabine Kaya, Christel Depienne, Maja Tarailo-Graovac, Karl Martin Klein
Summary: Familial adult myoclonic epilepsy (FAME) is a neurological disease characterized by cortical tremor, myoclonus, and seizures caused by pentanucleotide repeat expansion. The SAMD12 locus was associated with FAME in European patients, representing the shortest identified TTTCA expansion. Repeat-primed PCR (RP-PCR) may miss the underlying mutation, and genome sequencing may be needed to confirm the pathogenic repeat.
Article
Computer Science, Interdisciplinary Applications
Rosella Tro, Monica Roascio, Gabriele Arnulfo, Domenico Tortora, Mariasavina Severino, Andrea Rossi, Antonio Napolitano, Marco M. Fato
Summary: Choosing the most appropriate denoising method is crucial for improving the quality of diagnostic images in the pre-processing of diffusion MRI images. This study compared two adaptive techniques, Patch2Self and Nlsam, and found that Patch2Self framework is specifically suitable for DKI data, demonstrating better performance at 7T.
COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
(2023)
Article
Clinical Neurology
Sara Uccella, Alessandro Parodi, Maria Grazia Calevo, Lino Nobili, Domenico Tortora, Mariasavina Severino, Chiara Andreato, Andrea Rossi, Luca Antonio Ramenghi
Summary: This study aimed to determine the impact of isolated low-grade germinal matrix-intraventricular haemorrhages (LG-GMH-IVH) and low-grade punctate cerebellar haemorrhages (LG-CBH) on the neurodevelopment of infants born preterm with very low birthweight (VLBW). The results showed that both the LG-GMH-IVH and LG-CBH groups scored lower on the GMDS-ER assessments compared to the no-lesion group at all ages. Early rehabilitation may have contributed to the development of infants with LG-GMH-IVH, while it may have had a greater impact on the development of infants with LG-CBH.
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
(2023)
Review
Acoustics
Nevena Fileva, Mariasavina Severino, Domenico Tortora, Antonia Ramaglia, Dario Paladini, Andrea Rossi
Summary: Fetal MRI is a crucial tool for diagnosing brain malformations during prenatal stages, especially when ultrasound indicates a potential abnormality. Despite the immature state of the fetal brain, early signs of brain malformations can still be recognized. Differentiating between normal brain growth and pathological conditions can be challenging and requires extensive knowledge of the central nervous system's development and corresponding neuroradiological stages. This article provides a review of common second-trimester brain malformations, focusing on helpful tips and subtle signs to aid in the diagnosis of conditions such as rhombencephalosynapsis, vermian rotation, molar tooth spectrum anomalies, diencephalic-mesencephalic junction dysplasia, ganglionic eminence anomalies, and common malformations of cortical development.
JOURNAL OF CLINICAL ULTRASOUND
(2023)
Article
Biotechnology & Applied Microbiology
Si-Yue Yu, Tiffany Carlaw, Tyler Thomson, Alexandra Birkenshaw, Genc Basha, Daniel Kurek, Cassie Huang, Jayesh Kulkarni, Lin-Hua Zhang, Colin J. D. Ross
Summary: The development of CRISPR genome editing technology has potential for treating genetic diseases, but delivering genome editors to affected tissues is challenging. In this study, a luminescent ABE (LumA) mouse model was developed, which showed restoration of luciferase activity through A-to-G correction. The model was validated using FDA-approved lipid nanoparticle formulations and demonstrated successful restoration of luciferase activity in treated mice. This model can be used to evaluate the efficacy and safety of genome editors and delivery systems for optimizing genome editing therapeutics.
Article
Medicine, General & Internal
George Hadjidekov, Gleb Haynatzki, Petya Chaveeva, Miroslav Nikolov, Gabriele Masselli, Andrea Rossi
Summary: This study compared the 2D and 3D segmentation of fetal lateral ventricles and brain structures using ultrasound and MRI. The results showed that both ultrasound and MRI measurements were consistent and reliable, providing valuable information for clinical prognosis and patient counseling.
Article
Biotechnology & Applied Microbiology
Gherman Novakovsky, Oriol Fornes, Manu Saraswat, Sara Mostafavi, Wyeth W. W. Wasserman
Summary: ExplaiNN combines the expressiveness of CNNs with the interpretability of linear models, achieving comparable performance to state-of-the-art methods in predicting TF binding, chromatin accessibility, and de novo motifs. Its transparent predictions provide both global and local biological insights into the data. ExplaiNN serves as a plug-and-play platform for pretrained models and annotated position weight matrices, aiming to accelerate the adoption of deep learning in genomic sequence analysis by domain experts.
