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)
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
Genetics & Heredity
Yonghua Chen, Qingqing Chen, Ke Yuan, Jianfang Zhu, Yanlan Fang, Qingfeng Yan, Chunlin Wang
Summary: This study reported a novel pathogenic variant in the NIPBL gene associated with Cornelia de Lange syndrome (CdLS). The study also identified key regulatory sequences in the 5' untranslated region of NIPBL mRNA.
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
Chemistry, Multidisciplinary
Angel Matute-Llorente, Angela Ascaso, Ana Latorre-Pellicer, Beatriz Puisac, Laura Trujillano, Elena Llorente, Juan Jose Puente-Lanzarote, Ariadna Ayerza-Casas, Maria Arnedo, Luis A. Moreno, Feliciano Ramos, Juan Pie, Jose A. Casajus, Gloria Bueno-Lozano
Summary: This study evaluated bone health and body composition in individuals with Cornelia de Lange Syndrome using dual-energy X-ray absorptiometry. Most of the CdLS patients had potentially causative genetic variants in NIPBL based on deep sequencing. While bone health seemed less of a concern during childhood and adolescence, some individuals were at risk for impaired bone health in adulthood. Monitoring of calcium, phosphorus, vitamin D levels, and other biomarkers can help assess bone health in this population.
APPLIED SCIENCES-BASEL
(2021)
Review
Biochemistry & Molecular Biology
Pablo Garcia-Gutierrez, Mario Garcia-Dominguez
Summary: CdLS is a human developmental syndrome that may be a transcriptomopathy related to transcriptional regulation, altered cohesin complex function, and mutations in NIPBL. The pathogenesis of CdLS is likely primarily based on changes in gene expression programs.
FRONTIERS IN MOLECULAR BIOSCIENCES
(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
Jingrong Chen, Erin N. Floyd, Dean S. Dawson, Susannah Rankin
Summary: Cornelia de Lange Syndrome (CdLS) is a developmental disorder caused by mutations in genes encoding subunits or regulators of the cohesin complex. These mutations can affect chromosome architecture and lead to defects in sister chromatid cohesion, mitotic progression, and DNA damage sensitivity, contributing to the phenotypes seen in CdLS affected individuals.
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
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
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
Cell & Tissue Engineering
Alessandro Umbach, Giulia Maule, Eyemen Kheir, Alessandro Cutarelli, Marika Foglia, Luca Guarrera, Luca L. Fava, Luciano Conti, Enrico Garattini, Mineko Terao, Anna Cereseto
Summary: This study presents an efficient method of repairing the NIPBL gene using CRISPR-Cas and HDR induced by inhibiting NHEJ repair. The generated isogenic hiPSCs clones possess regular karyotype and preserved pluripotency.
STEM CELL RESEARCH & THERAPY
(2022)
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.
