Article
Biochemistry & Molecular Biology
Olga Shchagina, Mariya Orlova, Aisylu Murtazina, Alexandra Filatova, Mikhail Skoblov, Elena Dadali
Summary: The implementation of NGS methods in clinical practice is helpful for identifying the molecular cause of genetically heterogeneous diseases. Additional analysis is needed when there are potential causative variants to select the correct one. In this study, a family with HMSN type 1 was investigated, and DNA analysis revealed multiple variants in different genes, with one variant being pathogenic based on functional analysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Kaihui Zhang, Lili Kang, Haozheng Zhang, Lu Bai, Huanping Pang, Qinghua Liu, Xinyi Zhang, Dong Chen, Haihua Yu, Yuqiang Lv, Min Gao, Yi Liu, Zhongtao Gai, Dong Wang, Xiaoying Li
Summary: This study identified two novel compound heterozygous mutations in the PI4KA gene and diagnosed the child with a disease similar to gastrointestinal defects and immunodeficiency syndrome 2. The study also reported, for the first time, a synonymous mutation in the PI4KA gene that influences alternative splicing, expanding the understanding of PI4KIIIa deficiency-related diseases and providing important information for genetic counseling.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Engineering, Electrical & Electronic
Na Cheng, Huadong Wang, Xi Tang, Tao Zhang, Jie Gui, Chun-Hou Zheng, Junfeng Xia
Summary: In this study, a new method called EnDSM was proposed to accurately predict deleterious synonymous mutations by combining multiple features and machine learning algorithms. The results showed that EnDSM outperformed other predictors on both training and testing datasets. This research is of great importance for the prediction of synonymous mutations in the field of medical genomics.
IEEE TRANSACTIONS ON CIRCUITS AND SYSTEMS FOR VIDEO TECHNOLOGY
(2022)
Article
Genetics & Heredity
Ting Yu, Fan Yan, Yu Xu, Yufeng Hunag, Hongjian Gong, Peiwei Zhao, Dongming Sun, Yong Zhang, Furong Zhang, Xuelian He
Summary: This study reported a case of a rare genetic heart disease DCM2A and identified a novel variant in the TNNI3 gene through genetic sequencing analysis. Functional analysis suggested that this variant may be associated with the development of DCM.
Article
Clinical Neurology
Vera Fridman, Stefan Sillau, Jacob Bockhorst, Kaitlin Smith, Isabella Moroni, Emanuela Pagliano, Chiara Pisciotta, Guiseppe Piscosquito, Matilde Laura, Francesco Muntoni, Chelsea Bacon, Shawna Feely, Tiffany Grider, Laurie Gutmann, Rosemary Shy, Janel Wilcox, David N. Herrmann, Jun Li, Sindhu Ramchandren, Charlotte J. Sumner, Thomas E. Lloyd, John Day, Carly E. Siskind, Sabrina W. Yum, Reza Sadjadi, Richard S. Finkel, Steven S. Scherer, Davide Pareyson, Mary M. Reilly, Michael E. Shy
Summary: This study conducted a 5-year longitudinal natural history study on 139 patients with MPZ neuropathy and found that CMTES score was sensitive to changes in patients with axonal MPZ neuropathy but not in those with demyelinating forms. Patients with moderate baseline disease severity showed the greatest changes. These findings will inform future clinical trials of MPZ neuropathies.
ANNALS OF NEUROLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Avik Sarkar, Kalpana Panati, Venkata Ramireddy Narala
Summary: Precise pre-mRNA processing, including alternative splicing, is crucial for protein translation in eukaryotes. Both point mutations and synonymous mutations can affect the splicing process, with the latter influencing gene expression through various mechanisms. Different cis-acting elements and trans-acting splicing factors regulate splicing, and synonymous mutations in these elements can change the binding pattern of splicing factors, leading to aberrant splicing and the development of diseases.
MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH
(2022)
Article
Medicine, General & Internal
Haiyue Deng, Yanqin Zhang, Jie Ding, Fang Wang
Summary: This study evaluated the pathogenicity of COL4A3/COL4A4 variants detected by next-generation sequencing, and found that some variants affect RNA splicing, highlighting the importance of transcript analysis for better molecular diagnosis and genetic counselling of unclassified exonic sequence variants.
FRONTIERS IN MEDICINE
(2022)
Article
Clinical Neurology
Yi-Jun Chen, Zai-Qiang Zhang, Meng-Wen Wang, Yu-Sen Qiu, Ru-Ying Yuan, En-Lin Dong, Zhe Zhao, Hai-Tao Zhou, Ning Wang, Wan-Jin Chen, Xiang Lin
Summary: This study identified a novel ALDH18A1 gene mutation and demonstrated the value of splicing mutation prediction in characterizing disease-related intronic variants. The detected variant led to significantly decreased P5CS concentration in the proband's plasma compared to healthy controls. Furthermore, review of previously reported recessive cases indicated that SPG9B patients in this cohort presented with milder symptoms.
FRONTIERS IN NEUROLOGY
(2021)
Article
Anesthesiology
Alessia Peretti, Giovanna Squintani, Federica Taioli, Matteo Tagliapietra, Tiziana Cavallaro, Gian M. Fabrizi
Summary: Neuropathic pain is a common symptom in Charcot-Marie Tooth (CMT) disease and is related to A delta fibers impairment. The prevalence and types of pain vary among different CMT subtypes, and clinicians should be aware of this when managing the disease.
EUROPEAN JOURNAL OF PAIN
(2022)
Review
Pharmacology & Pharmacy
Brian C. Lin, Nayiri M. Kaissarian, Chava Kimchi-Sarfaty
Summary: Synonymous gene recoding, a method to substitute synonymous variants into genetic sequence, has been used to overcome production limitations in therapeutic development. However, evaluating the safety and efficacy of recoded therapeutics is challenging due to subtle but impactful changes in protein features caused by synonymous codon substitutions, requiring sensitive detection methods.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Genetics & Heredity
Eric Olinger, Intisar Al Alawi, Mohammed S. Al Riyami, Isa Al Salmi, Elisa Molinari, Eissa Ali Faqeih, Mohamed H. Al-Hamed, Miguel Barroso-Gil, Laura Powell, Abdulrahman A. Al-Hussaini, Khawla A. Rahim, Naif A. M. Almontashiri, Colin Miles, Shirlee Shril, Friedhelm Hildebrandt, Ian J. Wilson, John A. Sayer
Summary: The study identified the importance of synonymous NPHP3 variants in solving families with ciliopathy syndromes, which were previously discarded by pathogenicity pipelines. More careful reassessment of synonymous variants, especially rare ones in candidate genes, is warranted.
Article
Genetics & Heredity
Lihua Wang, Jianhui Sun, Shunshuai Ma, Junfeng Xia, Xiaoyan Li
Summary: Driver mutations in human cancers include not only missense mutations but also synonymous mutations. We have developed a computational method called PredDSMC to accurately predict driver synonymous mutations. The method utilizes multimodal features and feature selection, and outperforms state-of-the-art methods in differentiating driver synonymous mutations from passenger mutations.
FRONTIERS IN GENETICS
(2023)
Article
Genetics & Heredity
Pengzhen Jin, Kai Yan, Shaofen Ye, Yeqing Qian, Zaigui Wu, Miaomiao Wang, Yuqing Xu, Yanfei Xu, Minyue Dong
Summary: Synonymous mutations are generally considered non-pathogenic, but recent studies have shown that they can lead to abnormal splicing and affect protein function. This study identified a synonymous mutation in a Neurofibromatosis type I patient that caused abnormal splicing, confirming its pathogenicity.
FRONTIERS IN GENETICS
(2021)
Article
Clinical Neurology
Paige Howard, Shawna M. E. Feely, Tiffany Grider, Alexa Bacha, Marina Scarlato, Raffaella Fazio, Angelo Quattrini, Michael E. Shy, Stefano C. Previtali
Summary: Mutations in the Myelin Protein Zero (MPZ) gene lead to CMT1B, with toxic gain of function from the mutant protein causing neuropathy, while some patients have haploinsufficiency in the MPZ gene, mainly presenting with sensory neuropathy.
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2021)
Article
Genetics & Heredity
Fengchang Qiao, Cuiping Zhang, Yan Wang, Gang Liu, Binbin Shao, Ping Hu, Zhengfeng Xu
Summary: Cornelia de Lange syndrome is a genetically heterogeneous disorder with NIPBL gene variants accounting for a significant portion of cases. A new de novo synonymous variant in the NIPBL gene was identified through whole-exome sequencing, expanding the mutation spectrum and highlighting the crucial role of WES in identifying genetic variants. The study also underscores the importance of considering synonymous mutations as potential pathogenic variants in clinical diagnoses.
FRONTIERS IN GENETICS
(2021)
Article
Medicine, General & Internal
Eleonora Virgilio, Domizia Vecchio, Maria Francesca Sarnelli, Valentina Solara, Roberto Cantello, Cristoforo Comi
Summary: We conducted a retrospective analysis on MS patients with cognitive decline to investigate early predictors of future cognitive impairment and motor disability. Older and less educated patients with longer disease duration and higher white matter lesion load (WMLL) at diagnosis were more likely to develop cognitive impairment. WMLL, disease duration, and educational levels were significant predictive factors for future cognitive impairment.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Clinical Neurology
Mary M. Reilly, David N. Herrmann, Davide Pareyson, Steven S. Scherer, Richard S. Finkel, Stephan Zuechner, Joshua Burns, Michael E. Shy
Summary: Heritable neurological disorders provide insights into disease mechanisms, facilitating the development of novel therapeutic approaches. The challenges of measuring disease progression in rare and slowly progressive neurogenetic diseases are addressed through the development of clinical outcome assessments and disease biomarkers in inherited peripheral neuropathies. It is proposed that carefully developed biomarkers from imaging, plasma, or skin can predict meaningful progression in functional and patient-reported outcome assessments, enabling feasible clinical trials within a shorter duration for these rare and ultra-rare disorders.
ANNALS OF NEUROLOGY
(2023)
Article
Clinical Neurology
Christopher J. Record, Mariola Skorupinska, Matilde Laura, Alexander M. Rossor, Davide Pareyson, Chiara Pisciotta, Shawna M. E. Feely, Thomas E. Lloyd, Rita Horvath, Reza Sadjadi, David N. Herrmann, Jun Li, David Walk, Sabrina W. Yum, Richard A. Lewis, John Day, Joshua Burns, Richard S. Finkel, Mario A. Saporta, Sindhu Ramchandren, Michael D. Weiss, Gyula Acsadi, Vera Fridman, Francesco Muntoni, Roy Poh, James M. Polke, Stephan Zuchner, Michael E. Shy, Steven S. Scherer, Mary M. Reilly
Summary: This study collected demographic, clinical and genetic data on CMT patients with GJB1 variants and found that males are more severely affected than females. It also found that some reported GJB1 variants remain classified as variants of uncertain significance. By analyzing a large cohort, the study showed that enhanced variant interpretation increases the proportion of pathogenic variants in GJB1.
Article
Clinical Neurology
Tyler Rehbein, Tong Tong Wu, Simona Treidler, Davide Pareyson, Richard Lewis, Sabrina W. Yum, Brett A. McCray, Sindhu Ramchandren, Joshua Burns, Jun Li, Richard S. Finkel, Steven S. Scherer, Stephan Zuchner, Michael E. Shy, Mary M. Reilly, David N. Herrmann
Summary: Recessive SH3TC2 variants cause CMT4C, a disease with variable clinical characteristics. Longitudinal analysis of 56 patients showed that CMTES and CMTES-R scores were moderately responsive to change over 3 years, indicating their usefulness in assessing disease progression.
Article
Clinical Neurology
Chiara Pisciotta, Alessandro Bertini, Irene Tramacere, Fiore Manganelli, Gian Maria Fabrizi, Angelo Schenone, Stefano Tozza, Tiziana Cavallaro, Federica Taioli, Moreno Ferrarini, Marina Grandis, Emilia Bellone, Paola C. Mandich, Stefano Previtali, Yuri Falzone, Isabella Allegri, Luca Padua, Costanza Pazzaglia, Aldo Quattrone, Paola Valentino, Luca Gentile, Massimo Russo, Daniela Calabrese, Isabella Moroni, Emanuela Pagliano, Paola Saveri, Stefania Magri, Silvia Baratta, Franco Taroni, Anna Mazzeo, Lucio Santoro, Giuseppe Vita, Davide Pareyson, Italian CMT Network
Summary: Data from the Italian CMT Registry show that 1012 patients were registered, with 535 females, and 711 patients received a genetic diagnosis. The most common mutation was the PMP22 duplication (45.2%). CMT4A was the most severe type, followed by CMT4C and CMT1E. Foot deformities and walking difficulties were the main features. Shoe inserts and orthotic aids were used by almost one-half of all patients. Scoliosis was present in 20% of patients, especially in CMT4C.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Cell Biology
Federica Pezzuto, Francesca Lunardi, Luca Vedovelli, Gheorghe E. Olteanu, Francesco Fortarezza, Alessandro De Pellegrin, Luca Melan, Eleonora Faccioli, Elisa De Franceschi, Chiara Giraudo, Claudia del Vecchio, Serena Marinello, Giulia Pasello, Dario Gregori, Paolo Navalesi, Federico Rea, Marco Schiavon, Fiorella Calabrese
Summary: This study aims to analyze the lung lesions caused by SARS-CoV-2 infection and compare them with clinical data of lung cancer patients. The results showed that lung lesions in SARS-CoV-2 infected lung cancer patients were more severe compared to lung cancer patients without SARS-CoV-2 infection.
Article
Clinical Neurology
Miryam Carecchio, Michele Mainardi, Giulia Bonato
Summary: Primary familial brain calcification (PFBC), also known as Fahr's disease, is a rare neurodegenerative disease characterized by progressive bilateral calcification of the microvessels in the brain. The disease is caused by altered function of the Neurovascular Unit (NVU), leading to dysfunction of the blood-brain barrier and progressive neurodegeneration. Multiple genes have been identified as causative factors, and clinical presentation can vary from asymptomatic to movement disorders, cognitive decline, and psychiatric disturbances.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Chiara Benzoni, Marco Moscatelli, Laura Farina, Stefania Magri, Claudia Ciano, Vidmer Scaioli, Sara Alvera, Gabriella Cammarata, Stefania Bianchi-Marzoli, Massimo Castellani, Felicia Margherita Zito, Giorgio Marotta, Sylvie Piacentini, Alberto Villacara, Renato Mantegazza, Cinzia Gellera, Joao Duraes, Ana Gouveia, Anabela Matos, Maria do Carmo Macario, Davide Pareyson, Franco Taroni, Daniela Di Bella, Ettore Salsano
Summary: In this study, clinical and laboratory information of adult-onset leukodystrophy with vanishing white matter (LVWM) patients was reviewed. The study found that AO-LVWM presents varying clinical manifestations, including stroke-like events; white matter rarefaction is the most consistent diagnostic clue; cerebral glucose metabolic abnormalities and retinal alterations can be present; and LVWM might also be caused by a digenic inheritance affecting the eIF2B complex.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Roberto Gasparotti, Alessandro Salvalaggio, Daniele Corbo, Giorgio Agazzi, Mario Cacciavillani, Alessandro Lozza, Silvia Fenu, Grazia De Vigili, Matteo Tagliapietra, Gian Maria Fabrizi, Davide Pareyson, Laura Obici, Chiara Briani
Summary: Quantitative assessment of Magnetic Resonance Neurography (MRN) and Diffusion Tensor Imaging (DTI) of the sciatic nerve can reliably differentiate hereditary transthyretin amyloidosis (ATTRv) patients and pre-symptomatic carriers, providing a potential tool for early diagnosis and disease monitoring.
JOURNAL OF NEUROLOGY
(2023)
Letter
Clinical Neurology
Katy Eichinger, Steffen E. Behrens-Spraggins, Janet Sowden, Davide M. Pareyson, Mary S. Reilly, Steven E. Scherer, Michael N. Shy, David Herrmann
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2023)
Article
Clinical Neurology
Lorenzo Nanetti, Stefania Magri, Mario Fichera, Anna Castaldo, Anna Nigri, Chiara Pinardi, Alessia Mongelli, Lidia Sarro, Davide Pareyson, Marina Grisoli, Cinzia Gellera, Daniela Di Bella, Caterina Mariotti, Franco Taroni
Summary: This study identified a form of spinocerebellar ataxia (SCA) characterized by the presence of an intermediate-length expansion in the TATA-box binding protein gene (TBP40-46) and a pathogenic variant in the Stip1-homologous and U-Box containing protein 1 gene (STUB1), representing the first example of digenic inheritance in a cerebellar disorder. Patients with SCA(TBP/STUB1) exhibited multi-domain dementia and more severe impairment compared to those carrying only fully expanded SCA17 alleles. Neuroimaging analysis revealed reduced cerebellar volume and thickness in SCA(TBP/STUB1) patients, as well as basal ganglia volume reduction in both patient groups. The findings have implications for diagnosis and genetic counseling in families with hereditary and sporadic ataxia.
MOVEMENT DISORDERS
(2023)
Article
Medicine, General & Internal
Domizia Vecchio, Paolo Barbero, Giulia Galli, Eleonora Virgilio, Paola Naldi, Cristoforo Comi, Roberto Cantello
Summary: This study aimed to evaluate the prognostic role of visual evoked potentials (VEPs) of the non-neuritic eye at the diagnosis of multiple sclerosis (MS). The results showed that P100 latency and N75-P100 amplitude at MS diagnosis were associated with disability at last follow-up, and P100 latency was identified as a predictor for future disability.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Clinical Neurology
Marta Bellofatto, Luca Gentile, Alessandro Bertini, Irene Tramacere, Fiore Manganelli, Gian Maria Fabrizi, Angelo Schenone, Lucio Santoro, Tiziana Cavallaro, Marina Grandis, Stefano Previtali, Marina Scarlato, Isabella Allegri, Luca Padua, Costanza Pazzaglia, Flavio Villani, Eleonora Cavalca, Paola Saveri, Aldo Quattrone, Paola Valentino, Stefano Tozza, Massimo Russo, Anna Mazzeo, Giuseppe Vita, Sylvie Piacentini, Giuseppe Didato, Chiara Pisciotta, Davide Pareyson, CMT Network
Summary: This study investigated the presence of sleep abnormalities in Charcot-Marie-Tooth disease (CMT) patients and their correlation with disease severity and characteristics. The results showed that CMT patients had poor sleep quality and daytime somnolence, which were associated with anxiety, depression, and fatigue.
JOURNAL OF NEUROLOGY
(2023)
Article
Respiratory System
Fiorella Calabrese, Francesca Lunardi, Elisa Baldasso, Federica Pezzuto, Asuman Kilitci, Gheorghe-Emilian Olteanu, Claudia Del Vecchio, Francesco Fortarezza, Annalisa Boscolo, Marco Schiavon, Luca Vedovelli, Annamaria Cattelan, Dario Gregori, Federico Rea, Paolo Navalesi
Summary: The present study aims to comprehensively analyze the cellular components, inflammatory signature, and respiratory pathogens in bronchoalveolar lavage (BAL) of COVID-19-related acute respiratory distress syndrome (CARDS) patients. The results showed that CARDS patients had SARS-CoV-2 infection frequently associated with other respiratory pathogens, increased neutrophil granulocyte percentage, decreased interferon-gamma expression, and elevated levels of interleukins (IL)-1 beta and IL-9 in BAL. Age, IL-18 expression, and BAL neutrophilia were identified as the most important predictive variables for worse outcomes. This study provides important insights into the complex pathophysiology of CARDS through a comprehensive analysis of BAL.
RESPIRATORY RESEARCH
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Lucia Corrado, Fjorilda Caushi, Endri Visha, Beatrice Piola, Erica Melone, Diego Cotella, Laura Follia, Martina Tosi, Alessandro Pizzino, Ferdinando Clarelli, Domizia Vecchio, Massimo Filippi, Federica Esposito, Martinelli Boneschi Filippo Giovanni, Maurizio Leone, Nadia Barizzone, Sandra d'Alfonso
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)