Review
Biochemistry & Molecular Biology
Emily J. McFadden, Susan J. Baserga
Summary: The article introduces the function of a particular small nucleolar RNA (snoRNA), U8 snoRNA, which is essential for ribosomal RNA maturation. It also explores the dysregulation of U8 snoRNA in white matter disease and its impact on human brain function.
Article
Genetics & Heredity
Erik Rosenhahn, Thomas J. O'Brien, Maha S. Zaki, Ina Sorge, Dagmar Wieczorek, Kevin Rostasy, Antonio Vitobello, Sophie Nambot, Fowzan S. Alkuraya, Mais O. Hashem, Amal Alhashem, Brahim Tabarki, Abdullah S. Alamri, Ayat H. Al Safar, Dalal K. Bubshait, Nada F. Alahmady, Joseph G. Gleeson, Mohamed S. Abdel-Hamid, Nicole Lesko, Sofia Ygberg, Sandrina P. Correia, Anna Wredenberg, Shahryar Alavi, Seyed M. Seyedhassani, Mahya Ebrahimi Nasab, Haytham Hussien, Tarek E. Omar, Ines Harzallah, Renaud Touraine, Homa Tajsharghi, Heba Morsy, Henry Houlden, Mohammad Shahrooei, Maryam Ghavideldarestani, Ghada M. H. Abdel-Salam, Annalaura Torella, Mariateresa Zanobio, Gaetano Terrone, Nicola Brunetti-Pierri, Abdolmajid Omrani, Julia Hentschel, Johannes R. Lemke, Heinrich Sticht, Rami Abou Jamra, Andre E. X. Brown, Reza Maroofian, Konrad Platzer
Summary: This study identifies bi-allelic loss-of-function variants in the PPFIBP1 gene as a cause of severe neurodevelopmental disorder, characterized by early-onset epilepsy, microcephaly, and periventricular calcifications.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Clinical Neurology
Hong Jin, Xiaotun Ren, Husheng Wu, Yanqi Hou, Fang Fang
Summary: This report describes a genetically confirmed childhood case of LCC with compound heterozygous variants in the non-protein-coding gene SNORD118. The patient had the youngest onset age of LCC with a determined genotype. The triad cerebral-imaging findings of calcifications, cysts, and leukoencephalopathy provide a crucial diagnostic basis for LCC, and genetic assessment should be considered for diagnosis.
FRONTIERS IN NEUROLOGY
(2021)
Article
Multidisciplinary Sciences
Ryan M. Baxley, Wendy Leung, Megan M. Schmit, Jacob Peter Matson, Lulu Yin, Marissa K. Oram, Liangjun Wang, John Taylor, Jack Hedberg, Colette B. Rogers, Adam J. Harvey, Debashree Basu, Jenny C. Taylor, Alistair T. Pagnamenta, Helene Dreau, Jude Craft, Elizabeth Ormondroyd, Hugh Watkins, Eric A. Hendrickson, Emily M. Mace, Jordan S. Orange, Hideki Aihara, Grant S. Stewart, Edward Blair, Jeanette Gowen Cook, Anja-Katrin Bielinsky
Summary: MCM10 deficiency results in chronic replication stress, reducing cell viability due to increased genomic instability and telomere erosion. Loss of MCM10 function constrains telomerase activity, potentially leading to a build-up of abnormal replication structures and terminally-arrested replication forks that require processing by MUS81.
NATURE COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Reham Khalaf-Nazzal, James Fasham, Katherine A. Inskeep, Lauren E. Blizzard, Joseph S. Leslie, Matthew N. Wakeling, Nishanka Ubeyratna, Tadahiro Mitani, Jennifer L. Griffith, Wisam Baker, Fida' Al-Hijawi, Karen C. Keough, Alper Gezdirici, Loren Pena, Christine G. Spaeth, Peter D. Turnpenny, Joseph R. Walsh, Randall Ray, Amber Neilson, Evguenia Kouranova, Xiaoxia Cui, David T. Curiel, Davut Pehlivan, Zeynep Coban Akdemir, Jennifer E. Posey, James R. Lupski, William B. Dobyns, Rolf W. Stottmann, Andrew H. Crosby, Emma L. Baple
Summary: This study reveals that bi-allelic variants of CAMSAP1 cause a clinically recognizable neuronal migration disorder, characterized by craniofacial anomalies, microcephaly, neurodevelopmental delay, visual impairment, and seizures. The findings provide further understanding of the role of CAMSAP1 in neuronal migration and brain development.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Genetics & Heredity
Lore Pottie, Christin S. Adamo, Aude Beyens, Steffen Luetke, Piyanoot Tapaneeyaphan, Adelbert De Clercq, Phil L. Salmon, Riet De Rycke, Alper Gezdirici, Elif Yilmaz Gulec, Naz Khan, Jill E. Urquhart, William G. Newman, Kay Metcalfe, Stephanie Efthymiou, Reza Maroofian, Najwa Anwar, Shazia Maqbool, Fatima Rahman, Ikhlass Altweijri, Monerah Alsaleh, Sawsan Mohamed Abdullah, Mohammad Al-Owain, Mais Hashem, Henry Houlden, Fowzan S. Alkuraya, Patrick Sips, Gerhard Sengle, Bert Callewaert
Summary: Variants in LTBP1 result in a range of connective tissue and skeletal abnormalities in patients, particularly affecting the crucial processes of skin and bone ECM assembly and homeostasis.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Clinical Neurology
Chiara Kloeckner, J. Pedro Fernandez Murray, Mahtab Tavasoli, Heinrich Sticht, Gisela Stoltenburg-Didinger, Leila Motlagh Scholle, Somayeh Bakhtiari, Michael C. Kruer, Hossein Darvish, Saghar Ghasemi Firouzabadi, Alex Pagnozzi, Anju Shukla, Katta Mohan Girisha, Dhanya Lakshmi Narayanan, Parneet Kaur, Reza Maroofian, Maha S. Zaki, Mahmoud M. Noureldeen, Andreas Merkenschlager, Janina Gburek-Augustat, Elisa Cali, Selina Banu, Kamrun Nahar, Stephanie Efthymiou, Henry Houlden, Rami Abou Jamra, Jason Williams, Christopher R. McMaster, Konrad Platzer
Summary: The Kennedy pathways are important for the synthesis of cell membrane components and have been associated with neurodevelopmental disorders. The deficiency of CHKA is found to cause a severe neurodevelopmental disorder with epilepsy and microcephaly.
Article
Obstetrics & Gynecology
Ruyi Liu, Zheng Yan, Yong Fan, Ronggui Qu, Biaobang Chen, Bin Li, Ling Wu, Haibo Wu, Jian Mu, Lin Zhao, Wenjing Wang, Jie Dong, Yang Zeng, Qiaoli Li, Lei Wang, Qing Sang, Zhihua Zhang, Yanping Kuang
Summary: Our study identified bi-allelic variants in KCNU1 as novel pathogenetic genes for male infertility, particularly due to impaired sperm acrosome reactions. These findings were confirmed through functional studies and treatment strategies using a knock-in mouse model, where deficiencies were rescued through intracytoplasmic sperm injection.
HUMAN REPRODUCTION
(2022)
Article
Clinical Neurology
Isabell Cordts, Luisa Semmler, Jannik Prasuhn, Annette Seibt, Diran Herebian, Tharsini Navaratnarajah, Joohyun Park, Natalie Deininger, Lucia Laugwitz, Sophia L. Goericke, Paul Lingor, Norbert Brueggemann, Alexander Muenchau, Matthis Synofzik, Dagmar Timmann, Johannes A. Mayr, Tobias B. Haack, Felix Distelmaier, Marcus Deschauer
Summary: Bi-allelic variants in the COQ4 gene were found to cause an adult-onset ataxia-spasticity spectrum phenotype, and the disease course was milder than previously reported.
MOVEMENT DISORDERS
(2022)
Article
Medicine, Research & Experimental
Weijie Wang, Jing Guo, Juanzi Shi, Qun Li, Biaobang Chen, Zhiqi Pan, Ronggui Qu, Jing Fu, Rong Shi, Xia Xue, Jian Mu, Zhihua Zhang, Tianyu Wu, Wenjing Wang, Lin Zhao, Qiaoli Li, Lin He, Xiaoxi Sun, Qing Sang, Ge Lin, Lei Wang
Summary: PABPC1L gene variants are responsible for female infertility characterized by oocyte maturation arrest. These variants result in truncated proteins, reduced abundance, altered localization, and decreased mRNA translational activation. PABPC1L plays an important role in human oocyte maturation and could be a potential candidate gene for infertility causes.
EMBO MOLECULAR MEDICINE
(2023)
Article
Clinical Neurology
Hai-Lin Dong, Yin Ma, Hao Yu, Qiao Wei, Jia-Qi Li, Gong-Lu Liu, Hong-Fu Li, Lei Chen, Dian-Fu Chen, Ge Bai, Zhi-Ying Wu
Summary: This study identified an autosomal recessive sensory neuronopathy linked to pathogenic variants in the COX20 gene, which plays a vital role in mitochondrial complex IV assembly and is highly expressed in proprioceptive sensory neurons. Loss of COX20 contributes to mitochondrial bioenergetic dysfunction as a mechanism in peripheral sensory neuron disease.
Article
Obstetrics & Gynecology
Ann-Kristin Dicke, Jakob Albrethsen, Bradley L. Hoare, Margot J. Wyrwoll, Alexander S. Busch, Daniela Fietz, Adrian Pilatz, Clara Buehlmann, Anders Juul, Sabine Kliesch, Joerg Gromoll, Ross A. D. Bathgate, Frank Tuettelmann, Birgit Stallmeyer
Summary: This study reveals that bi-allelic loss-of-function variants in the INSL3 and RXFP2 genes are associated with bilateral cryptorchidism and male infertility, while heterozygous variant carriers are unaffected phenotypically. These findings have diagnostic value for patients with familial/bilateral cryptorchidism and shed light on the importance of INSL3 and RXFP2 in testicular descent and fertility.
HUMAN REPRODUCTION
(2023)
Article
Genetics & Heredity
Holger Hengel, Shabab B. Hannan, Sarah Dyack, Sara B. MacKay, Ulrich Schatz, Martin Fleger, Andreas Kurringer, Ghassan Balousha, Zaid Ghanim, Fowzan S. Alkuraya, Hamad Alzaidan, Hessa S. Alsaif, Tadahiro Mitani, Sevcan Bozdogan, Davut Pehlivan, James R. Lupski, Joseph J. Gleeson, Mohammadreza Dehghani, Mohammad Y. Mehrjardi, Elliott H. Sherr, Kendall C. Parks, Emanuela Argilli, Amber Begtrup, Hamid Galehdari, Osama Balousha, Gholamreza Shariati, Neda Mazaheri, Reza A. Malamiri, Alistair T. Pagnamenta, Helen Kingston, Siddharth Banka, Adam Jackson, Mathew Osmond, Angelika Riess, Tobias B. Haack, Thomas Naegele, Stefanie Schuster, Stefan Hauser, Jakob Admard, Nicolas Casadei, Ana Velic, Boris Macek, Stephan Ossowski, Henry Houlden, Reza Maroofian, Ludger Schoels
Summary: Loss-of-function variants in BCAS3 were found to cause a neurodevelopmental disorder, resulting in global developmental delay and various physical abnormalities in affected individuals. The human phenotype, though less severe compared to a mouse model, still highlights the crucial role of BCAS3 in neural tissue development.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Genetics & Heredity
Arisha Rasheed, Evren Gumus, Maha Zaki, Katherine Johnson, Humera Manzoor, Geneva LaForce, Danica Ross, Jennifer McEvoy-Venneri, Valentina Stanley, Sangmoon Lee, Abbir Virani, Tawfeg Ben-Omran, Joseph G. Gleeson, Sadaf Naz, Ashleigh Schaffer
Summary: Intellectual disability syndromes (IDSs) affect up to 3% of the world population, and a novel IDS segregating in five unrelated consanguineous families was clinically and genetically characterised in this study. The patients exhibited common clinical features including moderate-to-severe intellectual disability, corpus callosum agenesis, mild ventriculomegaly, simplified gyral pattern, cerebral atrophy, delayed motor and verbal milestones, and hypotonia. Four novel homozygous variants in TTC5 were identified, with one founder variant in Egypt. Missense variants disrupt highly conserved residues required for p300 interaction, while nonsense variants are predicted to decrease TTC5 expression.
JOURNAL OF MEDICAL GENETICS
(2021)
Article
Medicine, Research & Experimental
Kalliopi Sofou, Kolja Meier, Leslie E. Sanderson, Debora Kaminski, Laia Montoliu-Gaya, Emma Samuelsson, Maria Blomqvist, Lotta Agholme, Jutta Gaertner, Chris Muehlhausen, Niklas Darin, Tahsin Stefan Barakat, Lars Schlotawa, Tjakko van Ham, Jorge Asin Cayuela, Fredrik H. Sterky
Summary: Patients with lysosomal storage disease-like symptoms were found to have homozygous mutations in VPS16, resulting in impaired cellular functions such as transferrin uptake and lysosomal accumulation, which were rescued by re-expression of VPS16. Disrupted vps16 expression in zebrafish led to developmental defects and similar lysosomal and autophagosomal accumulation in the brain. This expands the understanding of diseases resulting from mutations in HOPS/CORVET subunits.
EMBO MOLECULAR MEDICINE
(2021)
Article
Clinical Neurology
Velda X. Han, Shekeeb S. Mohammad, Hannah F. Jones, Sushil Bandodkar, Yanick J. Crow, Russell C. Dale
Summary: In the treatment of Aicardi-Goutières syndrome (AGS), Janus kinase (JAK) 1 inhibition shows a precision medicine approach targeting type I interferon-mediated cell signaling. Elevated cerebrospinal fluid (CSF) neopterin levels in AGS patients decreased significantly in response to JAK inhibitors, indicating a potential role for CSF neopterin as a biomarker of treatment response.
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
(2022)
Article
Rheumatology
Kader Cetin Gedik, Lovro Lamot, Micol Romano, Erkan Demirkaya, David Piskin, Sofia Torreggiani, Laura A. Adang, Thais Armangue, Kathe Barchus, Devon R. Cordova, Yanick J. Crow, Russell C. Dale, Karen L. Durrant, Despina Eleftheriou, Elisa M. Fazzi, Marco Gattorno, Francesco Gavazzi, Eric P. Hanson, Min Ae Lee-Kirsch, Gina A. Montealegre Sanchez, Benedicte Neven, Simona Orcesi, Seza Ozen, M. Cecilia Poli, Elliot Schumacher, Davide Tonduti, Katsiaryna Uss, Daniel Aletaha, Brian M. Feldman, Adeline Vanderver, Paul A. Brogan, Raphaela Goldbach-Mansky
Summary: A Task Force developed "points to consider" for the diagnosis, treatment, and long-term monitoring of patients with rare immunodysregulatory diseases. These guidelines aim to standardize and improve care for patients with autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI, and AGS.
ANNALS OF THE RHEUMATIC DISEASES
(2022)
Article
Clinical Neurology
Hannah F. Jones, Marion Stoll, Gladys Ho, Dugald O'Neill, Velda X. Han, Simon Paget, Kirsty Stewart, Jennifer Lewis, Kavitha Kothur, Christopher Troedson, Yanick J. Crow, Russell C. Dale, Shekeeb S. Mohammad
Summary: This study reports three cases of spastic paraplegia or cerebral palsy caused by the ADAR c.3019G>A variant, which has incomplete penetrance and can mimic other diseases. A high level of clinical suspicion is required for diagnosis and treatment of this condition, which may be ameliorated by immunomodulatory therapy.
BRAIN & DEVELOPMENT
(2022)
Review
Pharmacology & Pharmacy
Siobhan Crilly, Emily McMahon, Paul R. Kasher
Summary: Zebrafish disease modeling has the potential to greatly improve the drug development pipeline for stroke. However, further development of the existing zebrafish stroke models and collaboration between zebrafish and stroke researchers are necessary for wider acceptance and incorporation of this system into translational stroke research.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Biochemistry & Molecular Biology
Marta M. Gabryelska, Andrew P. Badrock, Jian You Lau, Raymond T. O'Keefe, Yanick J. Crow, Grzegorz Kudla
Summary: RNA homodimerization plays an important role in various physiological processes, but lack of systematic in vivo detection methods has hindered our understanding. In this study, the researchers used CLASH, PARIS, and other RNA proximity ligation methods to detect RNA homodimers transcriptome-wide. They found that RNA:RNA homodimers mediated by direct base-pairing are rare across the human transcriptome, but enriched in specific transcripts. Furthermore, they discovered homodimerization of SARS-CoV-2 and Zika genomes, which may have implications for antiviral therapies.
Article
Immunology
Leslie Naesens, Josephine Nemegeer, Filip Roelens, Lore Vallaeys, Marije Meuwissen, Katrien Janssens, Patrick Verloo, Benson Ogunjimi, Dimitri Hemelsoet, Levi Hoste, Lisa Roels, Marieke De Bruyne, Elfride De Baere, Jo Van Dorpe, Amelie Dendooven, Anne Sieben, Gillian Rice, Tessa Kerre, Rudi Beyaert, Carolina Uggenti, Yanick J. Crow, Simon J. Tavernier, Jonathan Maelfait, Filomeen Haerynck
Summary: This study analyzed the clinical, genetic, and immunological characteristics of 3 patients with uncharacterized AGS. RNU7-1 gene mutations were found to impair the processing of RDH pre-mRNA. A distinct IFN-I signature was observed in peripheral blood, and MCP-1 (CCL2) and CXCL10 were upregulated in cerebrospinal fluid. Histopathological analysis showed thrombotic microangiopathy in kidney tissue. Dysregulated STAT phosphorylation was observed upon cytokine stimulation.
JOURNAL OF CLINICAL IMMUNOLOGY
(2022)
Article
Immunology
Marta Martin-Fernandez, Sofija Buta, Tom Le Voyer, Zhi Li, Lasse Toftdal Dynesen, Francoise Vuillier, Lina Franklin, Fatima Ailal, Alice Muglia Amancio, Louise Malle, Conor Gruber, Ibtihal Benhsaien, Jennie Altman, Justin Taft, Caroline Deswarte, Manon Roynard, Alejandro Nieto-Patlan, Kunihiko Moriya, Jeremie Rosain, Nathalie Boddaert, Aziz Bousfiha, Yanick J. Crow, Dragana Jankovic, Alan Sher, Jean-Laurent Casanova, Sandra Pellegrini, Jacinta Bustamante, Dusan Bogunovic
Summary: This study identifies a new USP18 mutation that leads to autoinflammation and mycobacterial disease due to insufficient negative regulation of IFN-I signaling, providing important insights into the underlying mechanism of specific interferonopathy.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Review
Urology & Nephrology
Lorenzo Lodi, Maria V. Mastrolia, Federica Bello, Giovanni M. Rossi, Maria L. Angelotti, Yanick J. Crow, Paola Romagnani, Augusto Vaglio
Summary: Type I interferon mediates tissue damage in kidney disorders, affecting the function of various renal cell types. These disorders can cause renal dysfunction and share pathological features. Defining the classification, pathogenic mechanisms, and histopathological patterns of IFN-I-related kidney disorders is crucial for diagnosis and treatment.
KIDNEY INTERNATIONAL
(2022)
Article
Rheumatology
Kader Cetin Gedik, Lovro Lamot, Micol Romano, Erkan Demirkaya, David Piskin, Sofia Torreggiani, Laura A. Adang, Thais Armangue, Kathe Barchus, Devon R. Cordova, Yanick J. Crow, Russell C. Dale, Karen L. Durrant, Despina Eleftheriou, Elisa M. Fazzi, Marco Gattorno, Francesco Gavazzi, Eric P. Hanson, Min Ae Lee-Kirsch, Gina A. Montealegre Sanchez, Benedicte Neven, Simona Orcesi, Seza Ozen, M. Cecilia Poli, Elliot Schumacher, Davide Tonduti, Katsiaryna Uss, Daniel Aletaha, Brian M. Feldman, Adeline Vanderver, Paul A. Brogan, Raphaela Goldbach-Mansky
Summary: This study aims to improve the diagnosis, treatment, and long-term monitoring of patients with autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI, and AGS. The research team developed guidelines and considerations to enhance care quality and disease outcomes.
ARTHRITIS & RHEUMATOLOGY
(2022)
Article
Immunology
Maud Tusseau, Ema Lovsin, Charlotte Samaille, Remi Pescarmona, Anne-Laure Mathieu, Maria-Cristina Maggio, Velma Selmanovic, Marusa Debeljak, Angelique Dachy, Gregor Novljan, Alexandre Janin, Louis Januel, Jean-Baptiste Gibier, Emilie Chopin, Isabelle Rouvet, David Goncalves, Nicole Fabien, Gillian Rice, Gaetan Lesca, Audrey Labalme, Paola Romagnani, Thierry Walzer, Sebastien Viel, Magali Perret, Yanick J. Crow, Tadej Avcin, Rolando Cimaz, Alexandre Belot
Summary: The interferon signaling in DNASE1L3 deficient patients is transient, unlike the anomalies observed in other diseases. DNASE1L3 deficiencies are associated with a broad phenotype including lupus nephritis and hypocomplementemic urticarial vasculitis.
JOURNAL OF CLINICAL IMMUNOLOGY
(2022)
Letter
Immunology
Yanick J. Crow
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Immunology
Sarah E. Withers, Charlie F. Rowlands, Victor S. Tapia, Frances Hedley, Ioana-Emilia Mosneag, Siobhan Crilly, Gillian I. Rice, Andrew P. Badrock, Andrew Hayes, Stuart M. Allan, Tracy A. Briggs, Paul R. Kasher
Summary: Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy characterized by excessive type I interferon (IFN-I) activity and upregulation of IFN-stimulated genes (ISGs). Zebrafish were investigated as an alternative model for studying AGS and a mutant zebrafish line recapitulating AGS5 was generated. The homozygous mutant zebrafish larvae exhibited neurological phenotypes, increased expression of ISGs, brain cell death, microcephaly, and locomotion deficits. Dysregulation of cholesterol biosynthesis was also observed in the zebrafish model and AGS patient whole blood, suggesting a potential role of cholesterol dysregulation in AGS pathophysiology.
FRONTIERS IN IMMUNOLOGY
(2023)
Editorial Material
Clinical Neurology
Siobhan Crilly, Marietta Zille, Paul R. Kasher, Michel Modo
FRONTIERS IN NEUROLOGY
(2023)
Review
Immunology
Yanick J. Crow, Daniel B. Stetson
Summary: The term 'type I interferonopathy' was coined 10 years ago to describe rare genetic diseases caused by aberrant upregulation of type I interferon signaling. Viral nucleic acid detection is crucial for effective immune response, but failure in self versus non-self discrimination can lead to Mendelian inborn errors of immunity characterized by upregulation of type I interferon signaling.
NATURE REVIEWS IMMUNOLOGY
(2022)