Review
Neurosciences
Ilaria Parenti, Frank J. Kaiser
Summary: Chromatinopathies are neurodevelopmental disorders caused by mutations in proteins responsible for chromatin remodeling and transcriptional regulation, resulting in dysregulation of gene expression and clinical features such as developmental delay and intellectual disability. CdLS is a typical example, primarily caused by mutations in cohesin complex subunits or regulators, but also by variants in non-cohesin genes with similar functions.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Melanie Panarotto, Iain F. Davidson, Gabriele Litos, Alexander Schleiffer, Jan-Michael Peters
Summary: Cornelia de Lange syndrome (CdLS) is a developmental multisystem disorder associated with NIPBL gene mutations. The study shows that NIPBL mutations impair the DNA loop extrusion activity of cohesin, which affects the interactions between developmental genes and their enhancers, potentially contributing to the etiology of CdLS.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Gabrielle Olley, Madapura M. Pradeepa, Graeme R. Grimes, Sandra Piquet, Sophie E. Polo, David R. FitzPatrick, Wendy A. Bickmore, Charlene Boumendil
Summary: Mutations in the BRD4 gene affect DNA damage signaling and perturb regulation of DNA repair in patients with Cornelia de Lange syndrome.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Paolo Grazioli, Chiara Parodi, Milena Mariani, Daniele Bottai, Elisabetta Di Fede, Aida Zulueta, Laura Avagliano, Anna Cereda, Romano Tenconi, Jolanta Wierzba, Raffaella Adami, Maria Iascone, Paola Francesca Ajmone, Thomas Vaccari, Cristina Gervasini, Angelo Selicorni, Valentina Massa
Summary: Cornelia de Lange Syndrome (CdLS) is a rare developmental disorder affecting multiple organs, with behavioral disturbances associated with abnormalities in brain structures of hindbrain embryonic origin. Activation of the canonical WNT pathway shows promise in rescuing the consistent phenotype in experimental models.
CELL DEATH DISCOVERY
(2021)
Article
Multidisciplinary Sciences
Felix D. Weiss, Lesly Calderon, Yi-Fang Wang, Radina Georgieva, Ya Guo, Nevena Cvetesic, Maninder Kaur, Gopuraja Dharmalingam, Ian D. Krantz, Boris Lenhard, Amanda G. Fisher, Matthias Merkenschlager
Summary: Cornelia de Lange Syndrome (CdLS) is a human developmental disorder caused by mutations affecting the function of cohesin, leading to cognitive impairment. Research shows deregulation of gene expression in CdLS patients and mouse models with cohesin depletion, which can be restored by re-expression of cohesin. These findings suggest that continuous requirement of cohesin for neuronal gene expression may underlie the intellectual disability in CdLS patients.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Silvana Pileggi, Marta La Vecchia, Elisa Adele Colombo, Laura Fontana, Patrizia Colapietro, Davide Rovina, Annamaria Morotti, Silvia Tabano, Giovanni Porta, Myriam Alcalay, Cristina Gervasini, Monica Miozzo, Silvia Maria Sirchia
Summary: This study investigated the impact of mutations in cohesin complex genes on chromatin architecture and imprinting network, particularly focusing on the IGF2/H19 locus. The results showed general impairment of chromatin architecture, emergence of new interactions, and dysregulation of the WNT pathway. The study provides new evidence on the effects of cohesin genetic defects on chromatin structure and epigenetic stability.
Article
Biotechnology & Applied Microbiology
Rie Seyama, Yuri Uchiyama, Jose Ricard Magliocco Ceroni, Veronica Eun Hue Kim, Isabel Furquim, Rachel Sayuri Honjo, Matheus Augusto Araujo Castro, Lucas Vieira Lacerda Pires, Hiromi Aoi, Kazuhiro Iwama, Kohei Hamanaka, Atsushi Fujita, Naomi Tsuchida, Eriko Koshimizu, Kazuharu Misawa, Satoko Miyatake, Takeshi Mizuguchi, Shintaro Makino, Atsuo Itakura, Debora R. Bertola, Chong Ae Kim, Naomichi Matsumoto
Summary: Recent studies have found significant overlap in transcript isoforms between brain tissue and Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs). Highly expressed cohesion-related genes in both brain and LCLs are associated with Cornelia de Lange Syndrome (CdLS). RNA sequencing of LCLs proved to be useful in identifying hidden variants in exome-negative cases, as several new pathogenic variants were identified using this method.
Article
Pediatrics
Vikas S. Gupta, Amir M. Khan, Ashley H. Ebanks, Pamela A. Lally, Kevin P. Lally, Matthew T. Harting
Summary: Cornelia de Lange syndrome (CdLS) is associated with congenital diaphragmatic hernia (CDH), resulting in poorer outcomes for CdLS patients. However, those with CdLS who undergo repair can survive to discharge. A significant proportion of CdLS patients do not undergo diaphragmatic repair, leading to higher mortality rates.
JOURNAL OF PEDIATRIC SURGERY
(2021)
Article
Genetics & Heredity
Maninder Kaur, Justin Blair, Batsal Devkota, Sierra Fortunato, Dinah Clark, Audrey Lawrence, Jiwoo Kim, Wonwook Do, Benjamin Semeo, Olivia Katz, Devanshi Mehta, Nobuko Yamamoto, Emma Schindler, Zayd Al Rawi, Nina Wallace, Jonathan J. Wilde, Jennifer McCallum, Jinglan Liu, Dongbin Xu, Marie McDonald, Stefan Rentas, Ahmad Abou Tayoun, Zhang Zhe, Omar Abdul-Rahman, Bill Allen, Moris A. Angula, Kwame Anyane-Yeboa, Jesus Argente, Pamela H. Arn, Linlea Armstrong, Lina Basel-Salmon, Gareth Baynam, Lynne M. Bird, Daniel Bruegger, Gaik-Siew Ch'ng, David Chitayat, Robin Clark, Gerald F. Cox, Usha Dave, Elfrede DeBaere, Michael Field, John M. Graham, Karen W. Gripp, Robert Greenstein, Neerja Gupta, Randy Heidenreich, Jodi Hoffman, Robert J. Hopkin, Kenneth L. Jones, Marilyn C. Jones, Ariana Kariminejad, Jillene Kogan, Baiba Lace, Julian Leroy, Sally Ann Lynch, Marie McDonald, Kirsten Meagher, Nancy Mendelsohn, Ieva Micule, John M. Toimie, Sheela Nampoothiri, Kaoru Ohashi, Cynthia M. Powell, Subhadra Ramanathan, Salmo Raskin, Elizabeth Roeder, Marlene Rio, Alan F. Rope, Karan Sangha, Angela E. Scheuerle, Adele Schneider, Stavit Shalev, Victoria Siu, Rosemarie Smith, Cathy Stevens, Tinatin Tkemaladze, John Toimie, Helga Toriello, Anne Turner, Patricia G. Wheeler, Susan M. White, Terri Young, Kathleen M. Loomes, Mary Pipan, Ann Tokay Harrington, Elaine Zackai, Ramakrishnan Rajagopalan, Laura Conlin, Matthew A. Deardorff, Deborah McEldrew, Juan Pie, Feliciano Ramos, Antonio Musio, Antonie D. Kline, Kosuke Izumi, Sarah E. Raible, Ian D. Krantz
Summary: Cornelia de Lange Syndrome (CdLS) is a rare developmental disorder characterized by variable manifestations of growth and developmental delays, involving multiple systems and caused by pathogenic variants in genes encoding cohesin complex proteins. The majority of cases are attributed to variants in the NIPBL gene. Other cohesin genes and additional genes such as ANKRD11, EP300, AFF4, TAF1, and BRD4 may also contribute to a CdLS-like phenotype. Understanding the genetic landscape of this population through comprehensive molecular analysis is essential for genotype-phenotype correlations and identification of novel candidate genes.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Yin Peng, Ying Zhu, Lin Wu, Fang Deng
Summary: This study reported a novel variant in the MAU2 gene in a Chinese patient with CdLS, strengthening the association between MAU2 variants and CdLS phenotypes. The study suggests that MAU2 should be included in the gene screening list for CdLS.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Jeremy D. Osko, Nicholas J. Porter, Christophe Decroos, Matthew S. Lee, Paris R. Watson, Sarah E. Raible, Ian D. Krantz, Matthew A. Deardorff, David W. Christianson
Summary: CdLS and associated spectrum disorders are characterized by congenital anomalies and linked to defects in the protein complex cohesin, with missense mutations in HDAC8 identified in children diagnosed with CdLS. The structure-function relationships of four mutations in HDAC8 have been outlined, shedding light on the importance of long-range interactions in the protein scaffold that can influence catalytic function.
JOURNAL OF STRUCTURAL BIOLOGY
(2021)
Review
Clinical Neurology
Ludovica Giani, Giovanni Michelini, Maria Nobile, Paola Francesca Ajmone, Paola Giovanna Vizziello, Simona Scaini
Summary: The social impairments in individuals with Cornelia de Lange Syndrome (CdLS) are mainly characterized by social anxiety, which differs from those observed in idiopathic autism. This systematic review examines the relationship between social anxiety and CdLS through cross-sectional comparisons, highlighting the importance of considering the nature of social demand and familiarity of the examiner in understanding social anxiety in CdLS individuals.
JOURNAL OF AFFECTIVE DISORDERS
(2022)
Article
Endocrinology & Metabolism
Yiding Shen, Dongyan Zhao, Long Sun, Xiuzhen Yang, Xiang Yan
Summary: Cornelia de Lange syndrome (CdLS) is a rare genetic disease with limited information on female genital abnormalities. Timely identification and treatment of genital abnormalities in female CdLS patients are crucial for symptom improvement, reducing complications, and controlling recurrent infections.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Genetics & Heredity
Ying Peng, Changbiao Liang, Hui Xi, Shuting Yang, Jiancheng Hu, Jialun Pang, Jing Liu, Yingchun Luo, Chengyuan Tang, Wanqin Xie, Hua Wang
Summary: Cornelia de Lange syndrome (CdLS) is a genetic disorder characterized by multisystemic malformations. This study presented clinical and genetic findings of three CdLS cases from separate Chinese families, showing associations between mutations in the NIPBL gene and CdLS.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
M. J. Pablo, P. Pamplona, M. Haddad, I Benavente, A. Latorre-Pellicer, M. Arnedo, L. Trujillano, G. Bueno-Lozano, L. M. Kerr, S. A. Huisman, F. J. Kaiser, F. Ramos, A. D. Kline, J. Pie, B. Puisac
Summary: This study found that autonomic nervous system dysfunction is present in many individuals with Cornelia de Lange Syndrome, which may be related to premature aging.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Genetics & Heredity
Romina Burla, Mariateresa Carcuro, Grazia D. Raffa, Alessandra Galati, Domenico Raimondo, Angela Rizzo, Mattia La Torre, Emanuela Micheli, Laura Ciapponi, Giovanni Cenci, Enrico Cundari, Antonio Musio, Annamaria Biroccio, Stefano Cacchione, Maurizio Gatti, Isabella Saggio
Review
Genetics & Heredity
Francesco Cucco, Antonio Musio
AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
(2016)
Article
Multidisciplinary Sciences
Francesca Cipressa, Patrizia Morciano, Giuseppe Bosso, Linda Mannini, Alessandra Galati, Grazia Daniela Raffa, Stefano Cacchione, Antonio Musio, Giovanni Cenci
NATURE COMMUNICATIONS
(2016)
Article
Biochemistry & Molecular Biology
Francesco Cucco, Elisa Palumbo, Serena Camerini, Barbara D'Alessio, Valentina Quarantotti, Maria Luisa Casella, Ilaria Maria Rizzo, Dubravka Cukrov, Domenico Delia, Antonella Russo, Marco Crescenzi, Antonio Musio
NUCLEIC ACIDS RESEARCH
(2018)
Article
Biochemistry & Molecular Biology
Dubravka Cukrov, Trent A. C. Newman, Megan Leask, Bryony Leeke, Patrizia Sarogni, Alessandra Patimo, Antonie D. Kline, Ian D. Krantz, Julia A. Horsfield, Antonio Musio
HUMAN MOLECULAR GENETICS
(2018)
Article
Genetics & Heredity
Antonie D. Kline, Ian D. Krantz, Masashige Bando, Katsuhiko Shirahige, Stephenson Chea, Toyonori Sakata, Suhas Rao, Dale Dorsett, Vijay Pratap Singh, Jennifer L. Gerton, Julia A. Horsfield, Anne L. Calof, Olivia Katz, Marco Grados, Sarah Raible, Kristin Baranano, Gholson Lyon, Antonio Musio, Cheri S. Carrico, Douglas K. Clemens, Patti Caudill, Valentina Massa, Bryan E. McGill, Aila Dommestrup, Julia O'Connor, Richard E. Haaland
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2019)
Article
Oncology
Patrizia Sarogni, Orazio Palumbo, Adele Servadio, Simonetta Astigiano, Barbara D'Alessio, Veronica Gatti, Dubravka Cukrov, Silvia Baldari, Maria Michela Pallotta, Paolo Aretini, Felice Dell'Orletta, Silvia Soddu, Massimo Carella, Gabriele Toietta, Ottavia Barbieri, Gabriella Fontanini, Antonio Musio
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2019)
Review
Genetics & Heredity
Patrizia Sarogni, Maria M. Pallotta, Antonio Musio
JOURNAL OF MEDICAL GENETICS
(2020)
Article
Cell Biology
Claudia Contadini, Laura Monteonofrio, Ilaria Virdia, Andrea Prodosmo, Davide Valente, Luciana Chessa, Antonio Musio, Luca L. Fava, Cinzia Rinaldo, Giuliana Di Rocco, Silvia Soddu
CELL DEATH & DISEASE
(2019)
Article
Biochemistry & Molecular Biology
Ana Latorre-Pellicer, Angela Ascaso, Laura Trujillano, Marta Gil-Salvador, Maria Arnedo, Cristina Lucia-Campos, Rebeca Antonanzas-Perez, Inigo Marcos-Alcalde, Ilaria Parenti, Gloria Bueno-Lozano, Antonio Musio, Beatriz Puisac, Frank J. Kaiser, Feliciano J. Ramos, Paulino Gomez-Puertas, Juan Pie
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Genetics & Heredity
Francesco Cucco, Patrizia Sarogni, Sara Rossato, Mirella Alpa, Alessandra Patimo, Ana Latorre, Cinzia Magnani, Beatriz Puisac, Feliciano J. Ramos, Juan Pie, Antonio Musio
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2020)
Article
Biochemistry & Molecular Biology
Stefano Barone, Patrizia Sarogni, Roberto Valli, Maria Michela Pallotta, Gazzi Silvia, Annalisa Frattini, Abdul Waheed Khan, Erika Rapalini, Cristiana Parri, Antonio Musio
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Review
Genetics & Heredity
Antonio Musio
Article
Biology
Chue Vin Chin, Jisha Antony, Sarada Ketharnathan, Anastasia Labudina, Gregory Gimenez, Kate M. Parsons, Jinshu He, Amee J. George, Maria Michela Pallotta, Antonio Musio, Antony Braithwaite, Parry Guilford, Ross D. Hannan, Julia A. Horsfield
Article
Genetics & Heredity
Antonie D. Kline, Ian D. Krantz, Matthew A. Deardorff, Katsuhiko Shirahige, Dale Dorsett, Jennifer L. Gerton, Meng Wu, Devanshi Mehta, Jason A. Mills, Cheri S. Carrico, Sarah Noon, Pamela S. Herrera, Julia A. Horsfield, Chiara Bettale, Jeremy Morgan, Sylvia A. Huisman, Jo Moss, Joseph McCleery, Marco Grados, Blake D. Hansen, Siddharth Srivastava, Emily Taylor-Snell, Lynne M. Kerr, Olivia Katz, Anne L. Calof, Antonio Musio, Alena Egense, Richard E. Haaland
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2017)