@article{7877,
  abstract     = {The NIPBL/MAU2 heterodimer loads cohesin onto chromatin. Mutations inNIPBLaccount for most cases ofthe rare developmental disorder Cornelia de Lange syndrome (CdLS). Here we report aMAU2 variant causing CdLS, a deletion of seven amino acids that impairs the interaction between MAU2 and the NIPBL N terminus.Investigating this interaction, we discovered that MAU2 and the NIPBL N terminus are largely dispensable fornormal cohesin and NIPBL function in cells with a NIPBL early truncating mutation. Despite a predicted fataloutcome of an out-of-frame single nucleotide duplication inNIPBL, engineered in two different cell lines,alternative translation initiation yields a form of NIPBL missing N-terminal residues. This form cannot interactwith MAU2, but binds DNA and mediates cohesin loading. Altogether, our work reveals that cohesin loading can occur independently of functional NIPBL/MAU2 complexes and highlights a novel mechanism protectiveagainst out-of-frame mutations that is potentially relevant for other genetic conditions.},
  author       = {Parenti, Ilaria and Diab, Farah and Gil, Sara Ruiz and Mulugeta, Eskeatnaf and Casa, Valentina and Berutti, Riccardo and Brouwer, Rutger W.W. and Dupé, Valerie and Eckhold, Juliane and Graf, Elisabeth and Puisac, Beatriz and Ramos, Feliciano and Schwarzmayr, Thomas and Gines, Macarena Moronta and Van Staveren, Thomas and Van Ijcken, Wilfred F.J. and Strom, Tim M. and Pié, Juan and Watrin, Erwan and Kaiser, Frank J. and Wendt, Kerstin S.},
  issn         = {22111247},
  journal      = {Cell Reports},
  number       = {7},
  publisher    = {Elsevier},
  title        = {{MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome}},
  doi          = {10.1016/j.celrep.2020.107647},
  volume       = {31},
  year         = {2020},
}

@article{7957,
  abstract     = {Neurodevelopmental disorders (NDDs) are a class of disorders affecting brain development and function and are characterized by wide genetic and clinical variability. In this review, we discuss the multiple factors that influence the clinical presentation of NDDs, with particular attention to gene vulnerability, mutational load, and the two-hit model. Despite the complex architecture of
mutational events associated with NDDs, the various proteins involved appear to converge on common pathways, such as synaptic plasticity/function, chromatin remodelers and the mammalian target of rapamycin (mTOR) pathway. A thorough understanding of the mechanisms behind these pathways will hopefully lead to the identification of candidates that could be targeted for treatment approaches.},
  author       = {Parenti, Ilaria and Garcia Rabaneda, Luis E and Schön, Hanna and Novarino, Gaia},
  issn         = {1878108X},
  journal      = {Trends in Neurosciences},
  number       = {8},
  pages        = {608--621},
  publisher    = {Elsevier},
  title        = {{Neurodevelopmental disorders: From genetics to functional pathways}},
  doi          = {10.1016/j.tins.2020.05.004},
  volume       = {43},
  year         = {2020},
}

@article{7149,
  abstract     = {In recent years, many genes have been associated with chromatinopathies classified as “Cornelia de Lange Syndrome‐like.” It is known that the phenotype of these patients becomes less recognizable, overlapping to features characteristic of other syndromes caused by genetic variants affecting different regulators of chromatin structure and function. Therefore, Cornelia de Lange syndrome diagnosis might be arduous due to the seldom discordance between unexpected molecular diagnosis and clinical evaluation. Here, we review the molecular features of Cornelia de Lange syndrome, supporting the hypothesis that “CdLS‐like syndromes” are part of a larger “rare disease family” sharing multiple clinical features and common disrupted molecular pathways.},
  author       = {Avagliano, Laura and Parenti, Ilaria and Grazioli, Paolo and Di Fede, Elisabetta and Parodi, Chiara and Mariani, Milena and Kaiser, Frank J. and Selicorni, Angelo and Gervasini, Cristina and Massa, Valentina},
  issn         = {1399-0004},
  journal      = {Clinical Genetics},
  number       = {1},
  pages        = {3--11},
  publisher    = {Wiley},
  title        = {{Chromatinopathies: A focus on Cornelia de Lange syndrome}},
  doi          = {10.1111/cge.13674},
  volume       = {97},
  year         = {2020},
}

@article{7488,
  abstract     = {Characteristic or classic phenotype of Cornelia de Lange syndrome (CdLS) is associated with a recognisable facial pattern. However, the heterogeneity in causal genes and the presence of overlapping syndromes have made it increasingly difficult to diagnose only by clinical features. DeepGestalt technology, and its app Face2Gene, is having a growing impact on the diagnosis and management of genetic diseases by analysing the features of affected individuals. Here, we performed a phenotypic study on a cohort of 49 individuals harbouring causative variants in known CdLS genes in order to evaluate Face2Gene utility and sensitivity in the clinical diagnosis of CdLS. Based on the profile images of patients, a diagnosis of CdLS was within the top five predicted syndromes for 97.9% of our cases and even listed as first prediction for 83.7%. The age of patients did not seem to affect the prediction accuracy, whereas our results indicate a correlation between the clinical score and affected genes. Furthermore, each gene presents a different pattern recognition that may be used to develop new neural networks with the goal of separating different genetic subtypes in CdLS. Overall, we conclude that computer-assisted image analysis based on deep learning could support the clinical diagnosis of CdLS.},
  author       = {Latorre-Pellicer, Ana and Ascaso, Ángela and Trujillano, Laura and Gil-Salvador, Marta and Arnedo, Maria and Lucia-Campos, Cristina and Antoñanzas-Pérez, Rebeca and Marcos-Alcalde, Iñigo and Parenti, Ilaria and Bueno-Lozano, Gloria and Musio, Antonio and Puisac, Beatriz and Kaiser, Frank J. and Ramos, Feliciano J. and Gómez-Puertas, Paulino and Pié, Juan},
  issn         = {14220067},
  journal      = {International Journal of Molecular Sciences},
  number       = {3},
  publisher    = {MDPI},
  title        = {{Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial phenotypes}},
  doi          = {10.3390/ijms21031042},
  volume       = {21},
  year         = {2020},
}