Article
Genetics & Heredity
Caroline Dias, Rolph Pfundt, Tjitske Kleefstra, Janneke Shuurs-Hoeijmakers, Elles M. J. Boon, Johanna M. van Hagen, Petra Zwijnenburg, Marjan M. Weiss, Boris Keren, Cyril Mignot, Arnaud Isapof, Karin Weiss, Tova Hershkovitz, Maria Iascone, Silvia Maitz, Rene G. Feichtinger, Dieter Kotzot, Johannes A. Mayr, Tawfeg Ben-Omran, Laila Mahmoud, Lynn S. Pais, Christopher A. Walsh, Vandana Shashi, Jennifer A. Sullivan, Nicholas Stong, Francois Lecoquierre, Anne-Marie Guerrot, Aude Charollais, Lance H. Rodan
Summary: Mutations in the TCF7L2 gene are associated with developmental delays, intellectual disabilities, eye problems, craniofacial abnormalities, and neuropsychiatric comorbidities such as autism and ADHD. However, most patients eventually achieve normal intelligence. Research on TCF7L2 variations will have significant implications for medical management and future studies.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2021)
Review
Cell Biology
Ana Marin-Quilez, Christian A. Di Buduo, Rocio Benito, Alessandra Balduini, Jose Rivera, Jose Maria Bastida
Summary: The GALE gene encodes an enzyme called UDP-galactose-4-epimerase, which plays a crucial role in the biosynthesis of glycoproteins and glycolipids. GALE-related disorders, such as galactosemia, are inherited in an autosomal recessive pattern and can lead to various complications. Recent studies have also linked GALE variants to severe thrombocytopenia and myelodysplastic syndrome.
Article
Genetics & Heredity
Elisa Cali, Mohnish Suri, Marcello Scala, Matteo P. Ferla, Shahryar Alavi, Eissa Ali Faqeih, Emilia K. Bijlsma, Kristen M. Wigby, Diana Baralle, Mohammad Y. Mehrjardi, Jennifer Schwab, Konrad Platzer, Katharina Steindl, Mais Hashem, Marilyn Jones, Dmitriy M. Niyazov, Jennifer Jacober, Rebecca Okashah Littlejohn, Denisa Weis, Neda Zadeh, Lance Rodan, Alice Goldenberg, Francois Lecoquierre, Marina Dutra-Clarke, Gabriella Horvath, Dana Young, Naama Orenstein, Shahad Bawazeer, Anneke T. Vulto-van Silfhout, Yvan Herenger, Mohammadreza Dehghani, Seyed Mohammad Seyedhassani, Amir Bahreini, Mahya E. Nasab, A. Gulhan Ercan-Sencicek, Zahra Firoozfar, Mojtaba Movahedinia, Stephanie Efthymiou, Pasquale Striano, Ehsan Ghayoor Karimiani, Vincenzo Salpietro, Jenny C. Taylor, Melody Redman, Alexander P. A. Stegmann, Andreas Laner, Ghada Abdel-Salam, Megan Li, Mario Bengala, Amelie Johanna Muller, Maria C. Digilio, Anita Rauch, Murat Gunel, Hannah Titheradge, Daniela N. Schweitzer, Alison Kraus, Irene Valenzuela, Scott D. McLean, Chanika Phornphutkul, Mustafa Salih, Amber Begtrup, Rhonda E. Schnur, Erin Torti, Tobias B. Haack, Carlos E. Prada, Fowzan S. Alkuraya, Henry Houlden, Reza Maroofian
Summary: PRMT7-related syndrome is a neurodevelopmental disorder characterized by short stature, intellectual developmental disability, hypotonia, brachydactyly, and distinct facial morphology. This study provides a comprehensive description of the clinical characteristics of this syndrome, contributing to a better understanding of the disease.
GENETICS IN MEDICINE
(2023)
Article
Genetics & Heredity
Beau D. E. Janssen, Marie-Jose H. van den Boogaard, Klaske Lichtenbelt, Eleanor G. Seaby, Karen Stals, Sian Ellard, Ruth Newbury-Ecob, Abhijit Dixit, Laura Roht, Sander Pajusalu, Katrin Ounap, Helen Firth, Michael Buckley, Meredith Wilson, Tony Roscioli, Timothy Tidwell, Rong Mao, Sarah Ennis, Sjoerd J. Holwerda, Koen van Gassen, Richard H. van Jaarsveld
Summary: TAF4 is identified as a novel dominant disease gene associated with neuro-developmental disorders (NDD) and is named T4NDD. It shares common features with other TAF-opathies related to TFIID subunits.
Article
Genetics & Heredity
Maria B. Christensen, Amanda M. Levy, Nazanin A. Mohammadi, Marcello Niceta, Rauan Kaiyrzhanov, Maria Lisa Dentici, Chadi Al Alam, Viola Alesi, Valerie Benoit, Kailash P. Bhatia, Tatjana Bierhals, Christian M. Bosselmann, Julien Buratti, Bert Callewaert, Berten Ceulemans, Perrine Charles, Matthias De Wachter, Mohammadreza Dehghani, Erika D'haenens, Martine Doco-Fenzy, Michaela Gessner, Cyrielle Gobert, Ulviyya Guliyeva, Tobias B. Haack, Trine B. Hammer, Tilman Heinrich, Maja Hempel, Theresia Herget, Ute Hoffmann, Judit Horvath, Henry Houlden, Boris Keren, Christina Kresge, Candy Kumps, Damien Lederer, Alban Lermine, Francesca Magrinelli, Reza Maroofian, Mohammad Yahya Vahidi Mehrjardi, Mahdiyeh Moudi, Amelie J. Mueller, Anna J. Oostra, Beth A. Pletcher, David Ros-Pardo, Shanika Samarasekera, Marco Tartaglia, Kristof Van Schil, Julie Vogt, Evangeline Wassmer, Juliane Winkelmann, Maha S. Zaki, Michael Zech, Holger Lerche, Francesca Clementina Radio, Paulino Gomez-Puertas, Rikke S. Moller, Zeynep Tuemer
Summary: Biallelic variants of the ZNF142 gene have been associated with intellectual disability, speech impairment, seizures, and movement disorders. This study expands on previous research by providing phenotype and genotype information of 26 individuals from 16 families. The clinical features of the individuals suggest a syndromic neurodevelopmental disorder with mild to moderate intellectual disability, language and gross motor development delays, seizures, hypotonia, behavioral features, movement disorders, and facial dysmorphism.
Article
Genetics & Heredity
Frederike L. Harms, Alexander J. M. Dingemans, Maja Hempel, Rolph Pfundt, Tatjana Bierhals, Christian Casar, Christian Mueller, Jikke-Mien F. Niermeijer, Jan Fischer, Arne Jahn, Christoph Huebner, Silvia Majore, Emanuele Agolini, Antonio Novelli, Jasper Van der Smagt, Robert Ernst, Ellen Van Binsbergen, Grazia M. S. Mancini, Marjon Van Slegtenhorst, Tahsin S. Barakat, Emma L. Wakeling, Arveen Kamath, Lilian Downie, Lynn Pais, Susan M. White, Bert B. A. de Vries, Kerstin Kutsche
Summary: In this study, we discovered that de novo variants in the PHF5A gene can cause developmental disorders. Through clinical, genomic, and functional studies, we identified various types of PHF5A variants in nine patients, including loss-of-function, missense, splice, and start-loss variants. Our findings suggest that the loss-of-function variants in PHF5A result in downregulation of genes involved in cell-cycle regulation, but compensatory mechanisms maintain normal levels of other SF3B complex components.
GENETICS IN MEDICINE
(2023)
Article
Genetics & Heredity
Riccardo Sangermano, Iris Deitch, Virginie G. Peter, Rola Ba-Abbad, Emily M. Place, Erin Zampaglione, Naomi E. Wagner, Anne B. Fulton, Luisa Coutinho-Santos, Boris Rosin, Vincent Dunet, Ala'a AlTalbishi, Eyal Banin, Ana Berta Sousa, Mariana Neves, Anna Larson, Mathieu Quinodoz, Michel Michaelides, Tamar Ben-Yosef, Eric A. Pierce, Carlo Rivolta, Andrew R. Webster, Gavin Arno, Dror Sharon, Rachel M. Huckfeldt, Kinga M. Bujakowska
Summary: The study validates the association between INPP5E gene mutations and non-syndromic IRD, as well as the wide phenotypic spectrum, demonstrating the involvement of genetic modifiers. Additionally, the research identifies 12 rare INPP5E variants not previously reported.
NPJ GENOMIC MEDICINE
(2021)
Article
Oncology
Isabel Castro, Belem Sampaio-Marques, Anabela C. Areias, Hugo Sousa, Angela Fernandes, Jose Manuel Sanchez-Maldonado, Cristina Cunha, Agostinho Carvalho, Juan Sainz, Paula Ludovico
Summary: Acute myeloid leukemia (AML) is a deadly blood cancer, with single nucleotide polymorphisms (SNPs) being considered as potential candidates for disease prevention. SNPs in the autophagy core gene ATG10, especially ATG10(rs3734114), are associated with increased susceptibility to AML. On the other hand, ATG10(rs1864182) SNP is linked to reduced risk of developing AML.
Article
Biochemistry & Molecular Biology
Sissy Bassani, Edward van Beelen, Mireille Rossel, Norine Voisin, Anna Morgan, Yoan Arribat, Nicolas Chatron, Jacqueline Chrast, Massimiliano Cocca, Benjamin Delprat, Flavio Faletra, Giuliana Giannuzzi, Nicolas Guex, Roxane Machavoine, Sylvain Pradervand, Jeroen J. Smits, Jiddeke M. van de Kamp, Alban Ziegler, Francesca Amati, Sandrine Marlin, Hannie Kremer, Heiko Locher, Tangui Maurice, Paolo Gasparini, Giorgia Girotto, Alexandre Reymond
Summary: Through exome sequencing and molecular assays, a novel autosomal dominant gene, USP48, has been identified as playing a crucial role in Non-Syndromic Hereditary Hearing Loss (NSHHL). Mutations in USP48 lead to impaired ability to hydrolyze tetra-ubiquitin. Immunohistology studies indicate expression of the encoded protein in the developing human inner ear, highlighting the role of USP48 in auditory function.
HUMAN MOLECULAR GENETICS
(2021)
Article
Genetics & Heredity
Shenzhao Lu, Rebecca Hernan, Paul C. Marcogliese, Yan Huang, Tracy S. Gertler, Meltem Akcaboy, Shiyong Liu, Hyung-lok Chung, Xueyang Pan, Xiaoqin Sun, Melahat Melek Oguz, Ulkuhan Oztoprak, Jeroen H. F. de Baaij, Jelena Ivanisevic, Erin McGinnis, Maria J. Guillen Sacoto, Wendy K. Chung, Hugo J. Bellen
Summary: This study shows that variants in the TIAM1 gene are associated with developmental delay, intellectual disability, speech delay, and seizures. The fruit fly ortholog of TIAM1, still life (sif), is found to be important for neural function. These findings provide the first evidence of the loss-of-function role of TIAM1 in the human nervous system.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Genetics & Heredity
Angelo Augusto M. Sumalde, Melissa A. Scholes, Olivia A. Kalmanson, Elizabeth A. Terhune, Lidia Frejo, Cambria I. Wethey, Pablo Roman-Naranjo, Patrick M. Carry, Samuel P. Gubbels, Jose A. Lopez-Escamez, Nancy Hadley-Miller, Regie Lyn P. Santos-Cortez
Summary: This study aimed to identify rare, coding variants in children with peripheral vertigo but no hearing loss, and in patients with potentially overlapping phenotypes, namely, Meniere's disease or idiopathic scoliosis. Rare variants were found in genes involved in migraine, musculoskeletal phenotypes, and vestibular development in children with vertigo. In addition, rare variants were also identified in adult patients with Meniere's disease and adolescents with lateral semicircular canal asymmetry and scoliosis. The study suggests that peripheral vestibular dysfunction in children may be caused by multiple rare variants within genes related to inner ear structure, migraine, and musculoskeletal disease.
Article
Hematology
Antoine Rimbert, Ming W. Yeung, Nawar Dalila, Chris H. L. Thio, Haojie Yu, Natalia Loaiza, Federico Oldoni, Adriaan van der Graaf, Siqi Wang, M. Abdullah Said, Lisanne L. Blauw, Aurore Girardeau, Lise Bray, Amandine Caillaud, Vincent W. Bloks, Marie Marrec, Philippe Mouli, Patrick C. N. Rensen, Bart van de Sluis, Harold Snieder, Mathilde Di Filippo, Pim van der Harst, Anne Tybjaerg-Hansen, Philippe Zimmerman, Bertrand Cariou, Jan Kuivenhoven
Summary: This study reveals that carriers of novel genetic variants of GPR146 have a favorable cardiometabolic risk profile. However, it remains unclear whether genetic or pharmaceutical inhibition of GPR146 can protect against atherosclerosis in humans.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Veterinary Sciences
Jennifer N. Kiser, Zeping Wang, Ricardo Zanella, Erik Scraggs, Mahesh Neupane, Bonnie Cantrell, Curtis P. Van Tassell, Stephen N. White, Jeremy F. Taylor, Holly L. Neibergs
Summary: This study identified putative causal mutations for disease susceptibility in Holstein and Jersey cattle related to MAP infection, suggesting that two specific SNPs may alter transcription and consequently susceptibility to MAP infection.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Review
Genetics & Heredity
Elvis Twumasi Aboagye, Samuel Mawuli Adadey, Edmond Wonkam-Tingang, Lucas Amenga-Etego, Gordon A. Awandare, Ambroise Wonkam
Summary: The genetic causes of non-syndromic hearing impairment are highly diverse, with over 124 distinct genes identified. This study aimed to systematically review the global distribution and origin of founder variants associated with hearing impairment.
Article
Dentistry, Oral Surgery & Medicine
Kai Sun, Miao Yu, Iting Yeh, Liutao Zhang, Haochen Liu, Tao Cai, Hailan Feng, Yang Liu, Dong Han
Summary: This study identified novel variants in the PAX9 gene and indicated that paired domain structural impairment and dominant-negative effect may be the underlying mechanisms of PAX9-related non-syndromic oligodontia.
Article
Genetics & Heredity
Allyn McConkie-Rosell, Kelly Schoch, Jennifer Sullivan, Rebecca C. Spillmann, Heidi Cope, Queenie K-G Tan, Christina G. S. Palmer, Stephen R. Hooper, Vandana Shashi
Summary: The Genome Empowerment Scale (GEmS) is a research tool to assess parents' perspectives on empowerment during exome or genome sequencing for children with undiagnosed disorders, with emotion-focused and action-oriented scales. The purpose of the study is to provide a strategy for interpreting GEmS results and present illustrative cases to guide genetic counseling for parents of children with undiagnosed conditions.
JOURNAL OF GENETIC COUNSELING
(2022)
Article
Developmental Biology
Yupu Wang, Meike Lobb-Rabe, James Ashley, Purujit Chatterjee, Veera Anand, Hugo J. Bellen, Oguz Kanca, Robert A. Carrillo
Summary: This study investigates the expression patterns of Dpr and DIP genes in different types of neurons in Drosophila, revealing unique combinations of these cell-surface proteins and providing insights into neural development and synaptic connectivity.
Editorial Material
Cell Biology
Hugo J. Bellen
Summary: Professor Hugo Bellen has made significant contributions to Drosophila genetics and the study of rare diseases. His lab plays a crucial role in diagnosing and treating (ultra)rare human diseases and provides advanced tools and technology for global research. In addition, he leads the Drosophila Gene Disruption Project and actively promotes translational model organism research.
DISEASE MODELS & MECHANISMS
(2022)
Article
Genetics & Heredity
J. Michael Harnish, Lucian Li, Sanja Rogic, Guillaume Poirier-Morency, Seon-Young Kim, Kym M. Boycott, Michael F. Wangler, Hugo J. Bellen, Philip Hieter, Paul Pavlidis, Zhandong Liu, Shinya Yamamoto
Summary: Next-generation sequencing is an important diagnostic tool for rare disease gene discovery. Collaboration between scientists, clinicians, and patients is crucial for resolving medical mysteries and understanding human gene function. Interaction between scientists and research funders can accelerate the translation of discoveries into therapeutic research.
Editorial Material
Biochemistry & Molecular Biology
Masamitsu Yamaguchi, Shinya Yamamoto
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Liping Wang, Guang Lin, Zhongyuan Zuo, Yarong Li, Seul Kee Byeon, Akhilesh Pandey, Hugo J. Bellen
Summary: Recessive variants in GBA1 can lead to Gaucher disease, a common lysosome storage disease. Using CRISPR-Cas9, we generated a null allele of the Drosophila ortholog Gba1b and found that it is expressed in glia but not in neurons. GlcCer is synthesized upon neuronal activity and transported from neurons to glia through exosomes. Glial TGF-beta/BMP induces GlcCer transfer from neurons to glia, and the White protein promotes GlcCer trafficking to glial lysosomes for degradation.
Article
Biochemistry & Molecular Biology
Hilman Nurmahdi, Mao Hasegawa, Elzava Yuslimatin Mujizah, Takeshi Sasamura, Mikiko Inaki, Shinya Yamamoto, Tomoko Yamakawa, Kenji Matsuno
Summary: Notch signaling is essential for cell-fate specification and involves direct cell-cell interactions. This study investigates the role of different epidermal growth factor (EGF)-like repeats in Notch receptor by analyzing 19 previously identified mutants. Findings suggest that certain EGF-like repeats may be crucial for proper folding and function of Notch protein.
Review
Clinical Neurology
T. J. Amrhein, J. W. Williams, L. Gray, M. D. Malinzak, S. Cantrell, C. R. Deline, C. M. Carr, D. K. Kim, K. M. Goldstein, P. G. Kranz
Summary: This study synthesized evidence on the efficacy of treatments for spontaneous intracranial hypotension (SIH), identified evidence gaps, and prioritized future research.
AMERICAN JOURNAL OF NEURORADIOLOGY
(2023)
Article
Cell Biology
Isha Ralhan, Jinlan Chang, Matthew J. Moulton, Lindsey D. Goodman, Nathanael Y. J. Lee, Greg Plummer, H. Amalia Pasolli, Doreen Matthies, Hugo J. Bellen, Maria S. Ioannou
Summary: During oxidative stress, neurons release lipids that are internalized by glia, and defects in this process are associated with neurodegenerative diseases. However, the mechanisms and consequences of lipid release on neuronal health are still unclear.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Genetics & Heredity
Sharayu Jangam, Lauren C. Briere, Kristy L. Jay, Jonathan C. Andrews, Melissa A. Walker, Lance H. Rodan, Frances A. High, Shinya Yamamoto, Michael F. Undiagnosed Diseases Network, David A. Sweetser, Michael F. Wangler
Summary: This study identifies a novel EZH1 variant associated with a neurodevelopmental disorder. Functional analysis in Drosophila suggests that this variant may have a gain-of-function effect.
Article
Clinical Neurology
J. L. Houk, S. Morrison, S. Peskoe, T. J. Amrhein, P. G. Kranz
Summary: This study aimed to assess the correlation between Bern scores and headache severity in patients with spontaneous intracranial hypotension. The results showed a low correlation between Bern scores and headache severity, suggesting that the imaging findings may not reliably reflect clinical severity.
AMERICAN JOURNAL OF NEURORADIOLOGY
(2023)
Article
Clinical Neurology
P. G. Kranz, M. D. Malinzak, L. Gray, J. Willhite, T. J. Amrhein
Summary: Resisted inspiration improves visualization of CSF-venous fistulas in most cases of spontaneous intracranial hypotension, but further investigation is needed to determine its impact on the overall diagnostic yield of myelography in this condition.
AMERICAN JOURNAL OF NEURORADIOLOGY
(2023)
Review
Genetics & Heredity
Shinya Yamamoto, Oguz Kanca, Michael F. Wangler, Hugo J. Bellen
Summary: This Review discusses the use of non-mammalian model organisms in genetic diagnosis of rare diseases, focusing on worms, flies, and zebrafish. The strategies, technologies, and approaches to using these models are explored, as well as their potential in understanding common disease mechanisms. Non-mammalian model organisms such as fruitflies, nematode worms, and zebrafish offer a quick and cost-effective way to study the effects of gene variants, which can be further validated in mammalian models and human cells. These studies have facilitated the diagnosis of numerous rare diseases and provided insights into common disease mechanisms and gene functions.
NATURE REVIEWS GENETICS
(2023)
Article
Genetics & Heredity
Cara P. Ford, Rebecca O. Littlejohn, Ryan German, Blake Vuocolo, Jose Aceves, Liesbeth Vossaert, Nichole Owen, Michael Wangler, Carrie A. Schmid, Texome Project
Summary: This study reports a case of a 7-year-old boy who was found to carry a pathogenic variant in a rare disease-related gene through whole-exome sequencing. The identification of this variant altered the patient's medical management and highlights the importance of implementing genomic medicine in underserved populations.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)