Article
Biochemistry & Molecular Biology
Gary J. Iacobucci, Beiying Liu, Han Wen, Brittany Sincox, Wenjun Zheng, Gabriela K. Popescu
Summary: This study investigates the pathogenic mechanism of two GluN2A variants and shows that the dynamic contact between residues P552 and F652 is critical for NMDA receptor activation. Both increased and reduced communication through this interaction cause dysfunction. These findings have important implications for understanding the functional abnormalities of the NMDA receptor.
MOLECULAR PSYCHIATRY
(2022)
Article
Medicine, General & Internal
Xun Wang, Dongni Wang, Qiwei Wang, Weiming Huang, Meimei Dongye, Xulin Zhang, Duoru Lin, Zhuoling Lin, Jing Li, Weiling Hu, Xiaoyan Li, Xiaoshan Lin, Qiuping Zhong, Weirong Chen, Haotian Lin
Summary: This study broadens the mutation and phenotype spectrum of the GJA8 and CHMP4B genes in a cohort of Chinese patients with congenital cataracts. Patients carrying mutations in the same gene exhibit similar cataract phenotypes at a young age.
FRONTIERS IN MEDICINE
(2021)
Article
Virology
Man Xing, Yihan Wang, Xinyu Wang, Jiaojiao Liu, Weiqian Dai, Gaowei Hu, Furong He, Qian Zhao, Ying Li, Lingjin Sun, Yuyan Wang, Shujuan Du, Zhongwei Dong, Chongjie Pang, Zhidong Hu, Xiaoyan Zhang, Jianqing Xu, Qiliang Cai, Dongming Zhou, Tom Gallagher
Summary: Developing broad-spectrum vaccines and optimal vaccination strategies is crucial to controlling the COVID-19 pandemic. In this study, a chimpanzee adenoviral vector-based COVID-19 vaccine was generated and its immune response was assessed in mice through different immunization routes. The results showed that the combined immunization routes elicited higher neutralizing antibody responses and induced comprehensive but distinct immune responses. This vaccine shows potential as a universal vaccination strategy.
JOURNAL OF VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Antonella Riva, Antonella Gambadauro, Valeria Dipasquale, Celeste Casto, Maria Domenica Ceravolo, Andrea Accogli, Marcello Scala, Giorgia Ceravolo, Michele Iacomino, Federico Zara, Pasquale Striano, Caterina Cuppari, Gabriella Di Rosa, Maria Concetta Cutrupi, Vincenzo Salpietro, Roberto Chimenz
Summary: MAC is a group of congenital eye anomalies that can affect one or both eyes. Variants in the KIF17 gene may be associated with microphthalmia and coloboma, highlighting a potential conserved role of this gene in eye development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Psychiatry
Lijie Dong, Yijing Wang, Xiaomeng Wang, Tengfei Luo, Qiao Zhou, Guihu Zhao, Bin Li, Lu Xia, Kun Xia, Jinchen Li
Summary: This study investigated the individual and combined effects of polygenic risk, damaging de novo variants (DNVs), and sex on the risk and clinical presentation of autism spectrum disorder (ASD) in 2,591 ASD simplex families. The findings revealed that both polygenic risk and damaging DNVs contribute to an increased risk for ASD, with females exhibiting higher genetic burdens than males. They also found that the effects of polygenic risk and damaging DNVs on autism broad phenotypes were inconsistent, and that females exhibited more severe cognitive and behavioral problems compared to males.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Immunology
Qinhai Ma, Man Li, Lin Ma, Caroline Zhang, Hong Zhang, Huiling Zhong, Jian Wen, Yongsheng Wang, Zewei Yan, Wei Xiong, Linping Wu, Jianmin Guo, Wei Yang, Zifeng Yang, Biliang Zhang
Summary: A novel bivalent mRNA vaccine, RBMRNA-405, was developed in this study, consisting of mRNA encoding both Delta and Omicron Spike proteins. The results showed that RBMRNA-405 vaccine could induce broad neutralizing antibody responses against various SARS-CoV-2 variants and effectively block infection and lung injury caused by Omicron and Delta variants, indicating its promising potential for clinical development.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Clinical Neurology
Andrea Accogli, Stacy Goergen, Giana Izzo, Kshitij Mankad, Karina Krajden Haratz, Cecilia Parazzini, Michael Fahey, Lara Menzies, Julia Baptista, Lucia Carpineta, Domenico Tortora, Ezio Fulcheri, Valerio Gaetano Vellone, Dario Paladini, Luigina Spaccini, Valentina Toto, Claire Trayers, Liat Ben Sira, Adi Reches, Gustavo Malinger, Vincenzo Salpietro, Patrizia De Marco, Myriam Srour, Federico Zara, Valeria Capra, Andrea Rossi, Mariasavina Severino
Summary: Data on fetal MRI in L1 syndrome are scarce, but two distinct patterns were identified in fetuses with L1CAM mutations, providing valuable insights for prenatal diagnosis and counseling.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Immunology
Rui Wang, Chunyun Sun, Juan Ma, Chulin Yu, Desheng Kong, Meng Chen, Xuejie Liu, Dandan Zhao, Shuman Gao, Shuyuan Kou, Lili Sun, Zeyong Ge, Jun Zhao, Kuokuo Li, Tao Zhang, Yanjing Zhang, Chunxia Luo, Xuefeng Li, Yang Wang, Liangzhi Xie
Summary: This study evaluated the efficacy of a bivalent vaccine based on SARS-CoV-2 variants Alpha and Beta in mouse immunogenicity studies. Compared to monovalent vaccines, the bivalent vaccine induced higher and broad-spectrum cross-neutralizing activities against various SARS-CoV-2 variants.
Article
Multidisciplinary Sciences
Nathan L. Absalom, Vivian W. Y. Liao, Katrine M. H. Johannesen, Elena Gardella, Julia Jacobs, Gaetan Lesca, Zeynep Gokce-Samar, Alexis Arzimanoglou, Shimriet Zeidler, Pasquale Striano, Pierre Meyer, Ira Benkel-Herrenbrueck, Inger-Lise Mero, Jutta Rummel, Mary Chebib, Rikke S. Moller, Philip K. Ahring
Summary: This study discovered that pathogenic mutations in the GABRB3 gene can be divided into gain-of-function and loss-of-function groups, with patients in each group displaying distinct clinical features. Patients with gain-of-function mutations had earlier age of seizure onset, higher risk of severe intellectual disability, more severe seizures, and poorer response to treatment. Febrile seizures at onset were exclusively found in patients with loss-of-function mutations.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Melissa M. Boerrigter, Rene H. M. te Morsche, Hanka Venselaar, Nikki Pastoors, Anja M. Geerts, Anne Hoorens, Joost P. H. Drenth
Summary: This study aimed to determine the pathogenicity of variants in a-1,3-glucosyltransferase (ALG8) in the autosomal dominant polycystic liver disease (ADPLD) population. Eight novel and one previously reported pathogenic variants in ALG8 were discovered in ADPLD individuals. ALG8-associated ADPLD exhibits a broad clinical spectrum, including the possibility of developing a small number of renal cysts.
Review
Neurosciences
Ana I. Silva, Friederike Ehrhart, Magnus O. Ulfarsson, Hreinn Stefansson, Kari Stefansson, Lawrence S. Wilkinson, Jeremy Hall, David E. J. Linden
Summary: Genomic copy number variants (CNVs) are associated with a high risk of neurodevelopmental disorders, and these high-risk genetic variants converge in common molecular pathways. Studies have shown that different CNVs have similar effects on core sensory, cognitive, and motor traits. Neuroimaging studies have provided valuable information on how CNVs affect brain structure and function. However, most studies only examine one CNV at a time, making it difficult to fully understand the extent of shared brain effects.
BIOLOGICAL PSYCHIATRY
(2022)
Article
Chemistry, Multidisciplinary
Ying Li, Shuxin Xu, Qing Ye, Hang Chi, Zhanchen Guo, Jingran Chen, Mei Wu, Baochao Fan, Bin Li, Cheng-Feng Qin, Zhen Liu
Summary: This study reports an unprecedented broad-spectrum antiviral strategy targeting viral glycan shields. By using hypervalent mannose-binding nanoparticles, the virus-receptor interaction can be blocked, viral aggregation can be induced, thereby inhibiting virus entry and facilitating virus phagocytosis. This strategy exhibits potent broad-spectrum antiviral efficacy against various viruses, including the novel coronavirus and its major variants, as well as other significant viruses.
Article
Chemistry, Multidisciplinary
Grazia Maugeri, Agata Grazia D'Amico, Velia D'Agata
Summary: PACAP is a neuropeptide with cytoprotective effects in the eye, particularly in the cornea, and may play a role in physiological or pathological conditions in the eye.
APPLIED SCIENCES-BASEL
(2022)
Article
Food Science & Technology
Fanqiang Meng, Xiaoyu Zhu, Haizhen Zhao, Ting Nie, Fengxia Lu, Zhaoxin Lu, Yingjian Lu
Summary: A novel class III bacteriocin gene, NX371, was identified and expressed from Lactobacillus acidophilus with significant antimicrobial activity against various foodborne pathogens. The study demonstrated that NX371 exhibited thermal and pH stability, effectively inhibiting the growth of pathogens in milk and cheese.
Article
Immunology
Charlotte Primard, Elodie Monchatre-Leroy, Judith Del Campo, Severine Valsesia, Elsa Nikly, Marion Chevandier, Franck Boue, Alexandre Servat, Marine Wasniewski, Evelyne Picard-Meyer, Thomas Courant, Nicolas Collin, Francisco J. Salguero, Alexandre Le Vert, Delphine Guyon-Gellin, Florence Nicolas
Summary: OVX033 is a novel vaccine candidate consisting of the full-length nucleocapsid (N) protein of SARS-CoV-2 genetically fused to a self-assembling domain called oligoDOM(®), which enhances antigen immunogenicity. It has demonstrated the ability to stimulate cross-reactive T cell responses and provide cross-protection against three variants of SARS-CoV-2 in a hamster challenge model, resulting in reduced weight loss, lower lung viral loads, and decreased lung histopathological lesions.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Genetics & Heredity
Ana Arteche-Lopez, Almudena Avila-Fernandez, Alejandra Damian, Emma Soengas-Gonda, Ruben Perez de la Fuente, Patricia Ramos Gomez, Jesus Gallego Merlo, Laura Horcajada Burgos, Carlos Cemillan Fernandez, Jose Miguel Lezana Rosales, Juan Francisco Gonzalez Martinez, Juan Francisco Quesada-Espinosa, Marta Corton, Maria Paz Guerrero-Molina
Summary: The biallelic pathogenic repeat expansion in the RFC1 gene is a recently discovered cause of CANVAS and late-onset ataxia. The c.724C > T p.(Arg242*) variant was found in compound heterozygosity with the pathogenic repeat expansion in two affected CANVAS sisters. Examining the RFC1 gene sequencing is important for the diagnosis of CANVAS, especially in patients with the AAGGG repeat expansion.
Article
Geriatrics & Gerontology
Marta Del Pozo-Valero, Marta Corton, Rosario Lopez-Rodriguez, Ignacio Mahillo-Fernandez, Javier Ruiz-Hornillos, Pablo Minguez, Cristina Villaverde, Maria Elena Perez-Tomas, Maria Barreda-Sanchez, Esther Mancebo, Estela Paz-Artal, Encarna Guillen-Navarro, Berta Almoguera, Carmen Ayuso
Summary: This study reveals the association between clonal hematopoiesis and mortality in COVID-19 patients, particularly showing a significant correlation between pathogenic/likely pathogenic clonal hematopoiesis and mortality in the 75-84 age group.
Article
Genetics & Heredity
Francisco Martinez-Granero, Elena Martinez-Cayuelas, Cristina Rodilla, Gonzalo Nunez-Moreno, Marta Rodriguez de Alba, Fiona Blanco-Kelly, Raquel Romero, Pablo Minguez, Carmen Ayuso, Isabel Lorda-Sanchez, Marta Corton, Berta Almoguera
Summary: Joubert syndrome (JS) is a clinically and genetically heterogeneous genetic disorder. We identified a novel biallelic intragenic duplication of exons 20-46 of CPLANE1 in a case of JS, which is the first report of such duplication as a potential molecular mechanism of JS. The diagnosis was confirmed by brain MRI showing the molar tooth sign, consistent with JS.
Article
Biochemistry & Molecular Biology
Alejandra Tamayo, Gonzalo Nunez-Moreno, Carolina Ruiz, Julie Plaisancie, Alejandra Damian, Jennifer Moya, Nicolas Chassaing, Patrick Calvas, Carmen Ayuso, Pablo Minguez, Marta Corton
Summary: PAX6 haploinsufficiency causes aniridia, a congenital eye disorder that involves the iris, and foveal hypoplasia. Comprehensive screening of the PAX6 locus revealed four deep-intronic variants with potential effects on pre-RNA splicing. Functional analysis using in vitro minigene splicing assays and nanopore-based long-read sequencing confirmed the impact of two variants on aberrant splicing, while the other two variants were found to have no effect on splicing. This study emphasizes the importance of integrating functional studies into diagnostic algorithms to achieve conclusive genetic diagnoses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lorena de la Fuente, Marta Del Pozo-Valero, Irene Perea-Romero, Fiona Blanco-Kelly, Lidia Fernandez-Caballero, Marta Corton, Carmen Ayuso, Pablo Minguez
Summary: Screening for pathogenic variants in rare genetic diseases has become more comprehensive with the use of whole exome and genome sequencing. However, the gene-disease associations are still not fully known. In this study, the researchers compiled functional networks and observed their varying ability to recover genes associated with different genetic diseases. They developed a network-based algorithm, GLOWgenes, which showed promising results in identifying new gene-disease associations, especially for less obvious ones.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Andrology
Rosario Lopez-Rodriguez, Javier Ruiz-Hornillos, Marta Corton, Berta Almoguera, Pablo Minguez, Maria Elena Perez-Tomas, Maria Barreda-Sanchez, Esther Mancebo, Lorena Ondo, Andrea Martinez-Ramas, Lidia Fernandez-Caballero, Juan Carlos Taracido-Fernandez, Antonio Herrero-Gonzalez, Ignacio Mahillo, Estela Paz-Artal, Encarna Guillen-Navarro, Carmen Ayuso
Summary: There is no association between the androgen receptor polyQ polymorphism and the severity of COVID-19 in male patients.
Article
Medicine, General & Internal
Naray Annamaria, Csidey Maria, Keki-Kovacs Klaudia, Nemeth Orsolya, Knezy Krisztina, Bausz Maria, Szigeti Andrea, Csorba Anita, Kormanyos Kitti, Szabo Dorottya, Stachon Tanja, Corton Marta, Tory Kalman, Nagy Zoltan Zsolt, Maka Erika, Szentmary Nora
Summary: The study aimed to determine the prevalence of ocular diseases in patients with congenital aniridia from a Hungarian center. Through examinations and detailed ophthalmological assessments of 82 patients, common ocular diseases associated with congenital aniridia were identified, including aniridia-associated keratopathy, secondary glaucoma, cataract, macular hypoplasia, and optic nerve head malformation. The findings highlight the need for systematic collaboration among different ophthalmological specialties to manage and care for these ocular abnormalities.
Article
Ophthalmology
Cristina Rodilla, Inmaculada Martin-Merida, Fiona Blanco-Kelly, Maria Jose Trujillo-Tiebas, Almudena Avila-Fernandez, Rosa Riveiro-Alvarez, Marta Del Pozo-Valero, Irene Perea-Romero, Saoud Tahsin Swafiri, Olga Zurita, Cristina Villaverde, Miguel Angel Lopez, Raquel Romero, Ionut Florin Iancu, Gonzalo Nunez-Moreno, Belen Jimenez-Rolando, Maria Pilar Martin-Gutierrez, Ester Carreno, Pablo Minguez, Blanca Garcia-Sandoval, Carmen Ayuso, Marta Corton
Summary: This study describes the genetic and clinical spectrum of QUCY2D-associated retinopathies and establishes their prevalence in a large cohort of patients. Four clinically different phenotypes were identified, and the different mutation types and disease onset differences associated with QUCY2D variants were determined. These findings are critical for defining cohorts for inclusion in future clinical trials.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2023)
Correction
Biochemistry & Molecular Biology
Yesim Kesim, Fabiola Ceroni, Alejandra Damian, Fiona Blanco-Kelly, Carmen Ayuso, Kathy Williamson, Veronique Paquis-Flucklinger, Dorine A. Bax, Julie Plaisancie, Claudine Rieubland, Mostafa Chamlal, Marta Corton, Nicolas Chassaing, Patrick Calvas, Nicola K. Ragge
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Yesim Kesim, Fabiola Ceroni, Alejandra Damian, Fiona Blanco-Kelly, Carmen Ayuso, Kathy Williamson, Veronique Paquis-Flucklinger, Dorine A. Bax, Julie Plaisancie, Claudine Rieubland, Mostafa Chamlal, Marta Corton, Nicolas Chassaing, Patrick Calvas, Nicola K. Ragge
Summary: Biallelic pathogenic variants in ALDH1A3 account for 11% of recessively inherited severe developmental eye anomalies. The relationship between ALDH1A3 variants and variable neurodevelopmental features remains unclear. This study describes seven unrelated families with biallelic pathogenic ALDH1A3 variants, confirming the consistent manifestation of bilateral anophthalmia/microphthalmia (A/M) with additional neurodevelopmental features and significant variability. Additionally, the study highlights the importance of screening ALDH1A3 variants in nonconsanguineous families with A/M and reports the first case with cataract.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Gonzalo Nunez-Moreno, Alejandra Tamayo, Carolina Ruiz-Sanchez, Marta Corton, Pablo Minguez
Summary: DNA variants altering pre-mRNA splicing are an underestimated cause of genetic diseases. Long-read sequencing is a suitable technique for identifying and quantifying mRNA isoforms. The VIsoQLR tool is described as an interactive analyzer, viewer, and editor for the identification and quantification of isoforms using long-read sequencing data, offering features such as editing splice sites through dynamic and interactive graphics and tables.
Article
Multidisciplinary Sciences
Erola Pairo-Castineira, Konrad Rawlik, Andrew D. Bretherick, Ting Qi, Yang Wu, Isar Nassiri, Glenn A. McConkey, Marie Zechner, Lucija Klaric, Fiona Griffiths, Wilna Oosthuyzen, Athanasios Kousathanas, Anne Richmond, Jonathan Millar, Clark D. Russell, Tomas Malinauskas, Ryan Thwaites, Kirstie Morrice, Sean Keating, David Maslove, Alistair Nichol, Malcolm G. Semple, Julian Knight, Manu Shankar-Hari, Charlotte Summers, Charles Hinds, Peter Horby, Lowell Ling, Danny McAuley, Hugh Montgomery, Peter J. M. Openshaw, Colin Begg, Timothy Walsh, Albert Tenesa, Carlos Flores, Jose A. Riancho, Augusto Rojas-Martinez, Pablo Lapunzina, Jian Yang, Chris P. Ponting, James F. Wilson, Veronique Vitart, Malak Abedalthagafi, Andre D. Luchessi, Esteban J. Parra, Raquel Cruz, Angel Carracedo, Angie Fawkes, Lee Murphy, Kathy Rowan, Alexandre C. Pereira, Andy Law, Benjamin Fairfax, Sara Clohisey Hendry, J. Kenneth Baillie
Summary: This study analyzed genetic data from 24,202 severe COVID-19 cases and identified potentially druggable targets, including inflammatory signaling, monocyte-macrophage activation and endothelial permeability, immunometabolism, and host factors required for viral entry and replication.