Maria Cristina Aspromonte

@article{Aspromonte2024D434,

title = {DisProt in 2024: improving function annotation of intrinsically disordered proteins},

author = { Maria Cristina Aspromonte and Maria Victoria Nugnes and Federica Quaglia and Adel Bouharoua and Silvio C.E. Tosatto and Damiano Piovesan and Vasileios Sagris and Vasilis J. Promponas and Anastasia Chasapi and Erzsébet Fichó and Galo E. Balatti and Gustavo Parisi and Martín González Buitrón and Gabor Erdos and Matyas Pajkos and Zsuzsanna Dosztányi and Laszlo Dobson and Alessio Del Conte and Damiano Clementel and Edoardo Salladini and Emanuela Leonardi and Fatemeh Kordevani and Hamidreza Ghafouri and Luiggi G. Tenorio Ku and Alexander Miguel Monzon and Carlo Ferrari and Zsófia Kálmán and Juliet F. Nilsson and Jaime Santos and Carlos Pintado-Grima and Salvador Ventura and Veronika Ács and Rita Pancsa and Mariane Goncalves Kulik and Miguel A. Andrade-Navarro and Pedro José Barbosa Pereira and Sonia Longhi and Philippe Le Mercier and Julian Bergier and Peter Tompa and Tamas Lazar},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85176208048&doi=10.1093%2fnar%2fgkad928&partnerID=40&md5=fc34ce08667ff42029fdb54d5142c08f},

doi = {10.1093/nar/gkad928},

issn = {03051048},

year  = {2024},

date = {2024-01-01},

journal = {Nucleic Acids Research},

volume = {52},

number = {D1},

pages = {D434 – D441},

publisher = {Oxford University Press},

abstract = {DisProt (URL: https://disprot.org) is the gold standard database for intrinsically disordered proteins and regions, providing valuable information about their functions. The latest version of DisProt brings significant advancements, including a broader representation of functions and an enhanced curation process. These improvements aim to increase both the quality of annotations and their coverage at the sequence level. Higher coverage has been achieved by adopting additional evidence codes. Quality of annotations has been improved by systematically applying Minimum Information About Disorder Experiments (MIADE) principles and reporting all the details of the experimental setup that could potentially influence the structural state of a protein. The DisProt database now includes new thematic datasets and has expanded the adoption of Gene Ontology terms, resulting in an extensive functional repertoire which is automatically propagated to UniProtKB. Finally, we show that DisProt’s curated annotations strongly correlate with disorder predictions inferred from AlphaFold2 pLDDT (predicted Local Distance Difference Test) confidence scores. This comparison highlights the utility of DisProt in explaining apparent uncertainty of certain well-defined predicted structures, which often correspond to folding-upon-binding fragments. Overall, DisProt serves as a comprehensive resource, combining experimental evidence of disorder information to enhance our understanding of intrinsically disordered proteins and their functional implications. © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.},

note = {Cited by: 15; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Quaglia2024,

title = {Best practices for the manual curation of intrinsically disordered proteins in DisProt},

author = { Federica Quaglia and Anastasia Chasapi and Maria Victoria Nugnes and Maria Cristina Aspromonte and Emanuela Leonardi and Damiano Piovesan and Silvio C.E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85188297172&doi=10.1093%2fdatabase%2fbaae009&partnerID=40&md5=df4fca19479789139b3fd19bb35c817f},

doi = {10.1093/database/baae009},

issn = {17580463},

year  = {2024},

date = {2024-01-01},

journal = {Database},

volume = {2024},

publisher = {Oxford University Press},

abstract = {The DisProt database is a resource containing manually curated data on experimentally validated intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) from the literature. Developed in 2005, its primary goal was to collect structural and functional information into proteins that lack a fixed three-dimensional structure.Today, DisProt has evolved into a major repository that not only collects experimental data but also contributes to our understanding of the IDPs/IDRs roles in various biological processes, such as autophagy or the life cycle mechanisms in viruses or their involvement in diseases (such as cancer and neurodevelopmental disorders). DisProt offers detailed information on the structural states of IDPs/IDRs, including state transitions, interactions and their functions, all provided as curated annotations. One of the central activities of DisProt is the meticulous curation of experimental data from the literature. For this reason, to ensure that every expert and volunteer curator possesses the requisite knowledge for data evaluation, collection and integration, training courses and curation materials are available. However, biocuration guidelines concur on the importance of developing robust guidelines that not only provide critical information about data consistency but also ensure data acquisition.This guideline aims to provide both biocurators and external users with best practices for manually curating IDPs and IDRs in DisProt. It describes every step of the literature curation process and provides use cases of IDP curation within DisProt. © The Author(s) 2024. Published by Oxford University Press.},

note = {Cited by: 1; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ghafouri2024D536,

title = {PED in 2024: improving the community deposition of structural ensembles for intrinsically disordered proteins},

author = { Hamidreza Ghafouri and Tamas Lazar and Alessio Del Conte and Luiggi G. Tenorio Ku and Peter Tompa and Silvio C.E. Tosatto and Alexander Miguel Monzon and Maria C. Aspromonte and Pau Bernadó and Belén Chaves-Arquero and Lucia Beatriz Chemes and Damiano Clementel and Tiago N. Cordeiro and Carlos A. Elena-Real and Michael Feig and Isabella C. Felli and Carlo Ferrari and Julie D. Forman-Kay and Tiago Gomes and Frank Gondelaud and Claudiu C. Gradinaru and Tâp Ha-Duong and Teresa Head-Gordon and Pétur O. Heidarsson and Giacomo Janson and Gunnar Jeschke and Emanuela Leonardi and Zi Hao Liu and Sonia Longhi and Xamuel L. Lund and Maria J. Macias and Pau Martin-Malpartida and Davide Mercadante and Assia Mouhand and Gabor Nagy and María Victoria Nugnes and José Manuel Pérez-Cañadillas and Giulia Pesce and Roberta Pierattelli and Damiano Piovesan and Federica Quaglia and Sylvie Ricard-Blum and Paul Robustelli and Amin Sagar and Edoardo Salladini and Lucile Sénicourt and Nathalie Sibille and João M.C. Teixeira and Thomas E. Tsangaris and Mihaly Varadi},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85181761325&doi=10.1093%2fnar%2fgkad947&partnerID=40&md5=0ad51562357f3e5f603d744e02f8729a},

doi = {10.1093/nar/gkad947},

issn = {03051048},

year  = {2024},

date = {2024-01-01},

journal = {Nucleic Acids Research},

volume = {52},

number = {D1},

pages = {D536 – D544},

publisher = {Oxford University Press},

abstract = {The Protein Ensemble Database (PED) (URL: https://proteinensemble.org) is the primary resource for depositing structural ensembles of intrinsically disordered proteins. This updated version of PED reflects advancements in the field, denoting a continual expansion with a total of 461 entries and 538 ensembles, including those generated without explicit experimental data through novel machine learning (ML) techniques. With this significant increment in the number of ensembles, a few yet-unprecedented new entries entered the database, including those also determined or refined by electron paramagnetic resonance or circular dichroism data. In addition, PED was enriched with several new features, including a novel deposition service, improved user interface, new database cross-referencing options and integration with the 3D-Beacons network—all representing efforts to improve the FAIRness of the database. Foreseeably, PED will keep growing in size and expanding with new types of ensembles generated by accurate and fast ML-based generative models and coarse-grained simulations. Therefore, among future efforts, priority will be given to further develop the database to be compatible with ensembles modeled at a coarse-grained level. © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.},

note = {Cited by: 12; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Piovesan2023D438,

title = {MobiDB: 10 years of intrinsically disordered proteins},

author = { Damiano Piovesan and Alessio Del Conte and Damiano Clementel and Alexander Miguel Monzon and Martina Bevilacqua and Maria Cristina Aspromonte and Javier A Iserte and Fernando E Orti and Cristina Marino-Buslje and Silvio C. E Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85145966264&doi=10.1093%2fnar%2fgkac1065&partnerID=40&md5=8547b341a7698891915b9e425ab793e7},

doi = {10.1093/nar/gkac1065},

issn = {03051048},

year  = {2023},

date = {2023-01-01},

journal = {Nucleic Acids Research},

volume = {51},

number = {1 D},

pages = {D438 – D444},

publisher = {Oxford University Press},

abstract = {The MobiDB database (URL: https://mobidb.org/) is a knowledge base of intrinsically disordered proteins. MobiDB aggregates disorder annotations derived from the literature and from experimental evidence along with predictions for all known protein sequences. MobiDB generates new knowledge and captures the functional significance of disordered regions by processing and combining complementary sources of information. Since its first release 10 years ago, the MobiDB database has evolved in order to improve the quality and coverage of protein disorder annotations and its accessibility. MobiDB has now reached its maturity in terms of data standardization and visualization. Here, we present a new release which focuses on the optimization of user experience and database content. The major advances compared to the previous version are the integration of AlphaFoldDB predictions and the re-implementation of the homology transfer pipeline, which expands manually curated annotations by two orders of magnitude. Finally, the entry page has been restyled in order to provide an overview of the available annotations along with two separate views that highlight structural disorder evidence and functions associated with different binding modes. © 2023 The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.},

note = {Cited by: 61; All Open Access, Gold Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Aleksander2023,

title = {The Gene Ontology knowledgebase in 2023},

author = { Suzi A. Aleksander and James Balhoff and Seth Carbon and J. Michael Cherry and Harold J. Drabkin and Dustin Ebert and Marc Feuermann and Pascale Gaudet and Nomi L. Harris and David P. Hill and Raymond Lee and Huaiyu Mi and Sierra Moxon and Christopher J. Mungall and Anushya Muruganugan and Tremayne Mushayahama and Paul W. Sternberg and Paul D. Thomas and Kimberly Van Auken and Jolene Ramsey and Deborah A. Siegele and Rex L. Chisholm and Petra Fey and Maria Cristina Aspromonte and Maria Victoria Nugnes and Federica Quaglia and Silvio Tosatto and Michelle Giglio and Suvarna Nadendla and Giulia Antonazzo and Helen Attrill and Gil Dos Santos and Steven Marygold and Victor Strelets and Christopher J. Tabone and Jim Thurmond and Pinglei Zhou and Saadullah H. Ahmed and Praoparn Asanitthong and Diana Luna Buitrago and Meltem N. Erdol and Matthew C. Gage and Mohamed Ali Kadhum and Kan Yan Chloe Li and Miao Long and Aleksandra Michalak and Angeline Pesala and Armalya Pritazahra and Shirin C. C. Saverimuttu and Renzhi Su and Kate E. Thurlow and Ruth C Lovering and Colin Logie and Snezhana Oliferenko and Judith Blake and Karen Christie and Lori Corbani and Mary E. Dolan and Li Ni and Dmitry Sitnikov and Cynthia Smith and Alayne Cuzick and James Seager and Laurel Cooper and Justin Elser and Pankaj Jaiswal and Parul Gupta and Sushma Naithani and Manuel Lera-Ramirez and Kim Rutherford and Valerie Wood and Jeffrey L. De Pons and Melinda R. Dwinell and G. Thomas Hayman and Mary L. Kaldunski and Anne E. Kwitek and Stanley J. F. Laulederkind and Marek A. Tutaj and Mahima Vedi and Shur-Jen Wang and Peter D'Eustachio and Lucila Aimo and Kristian Axelsen and Alan Bridge and Nevila Hyka-Nouspikel and Anne Morgat and Stacia R. Engel and Kalpana Karra and Stuart R. Miyasato and Robert S. Nash and Marek S. Skrzypek and Shuai Weng and Edith D. Wong and Erika Bakker and Tanya Z. Berardini and Leonore Reiser and Andrea Auchincloss and Ghislaine Argoud-Puy and Marie-Claude Blatter and Emmanuel Boutet and Lionel Breuza and Cristina Casals-Casas and Elisabeth Coudert and Anne Estreicher and Maria Livia Famiglietti and Arnaud Gos and Nadine Gruaz-Gumowski and Chantal Hulo and Florence Jungo and Philippe Le Mercier and Damien Lieberherr and Patrick Masson and Ivo Pedruzzi and Lucille Pourcel and Sylvain Poux and Catherine Rivoire and Shyamala Sundaram and Alex Bateman and Emily Bowler-Barnett and Hema Bye-A-Jee and Paul Denny and Alexandr Ignatchenko and Rizwan Ishtiaq and Antonia Lock and Yvonne Lussi and Michele Magrane and Maria J. Martin and Sandra Orchard and Pedro Raposo and Elena Speretta and Nidhi Tyagi and Kate Warner and Rossana Zaru and Alexander D. Diehl and Juancarlos Chan and Stavros Diamantakis and Daniela Raciti and Magdalena Zarowiecki and Malcolm Fisher and Christina James-Zorn and Virgilio Ponferrada and Aaron Zorn and Sridhar Ramachandran and Leyla Ruzicka and Monte Westerfield},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85164785564&doi=10.1093%2fgenetics%2fiyad031&partnerID=40&md5=d315a8c84634510d971d9d805f26769d},

doi = {10.1093/genetics/iyad031},

issn = {00166731},

year  = {2023},

date = {2023-01-01},

journal = {Genetics},

volume = {224},

number = {1},

publisher = {Oxford University Press},

abstract = {The Gene Ontology (GO) knowledgebase (http://geneontology.org) is a comprehensive resource concerning the functions of genes and gene products (proteins and noncoding RNAs). GO annotations cover genes from organisms across the tree of life as well as viruses, though most gene function knowledge currently derives from experiments carried out in a relatively small number of model organisms. Here, we provide an updated overview of the GO knowledgebase, as well as the efforts of the broad, international consortium of scientists that develops, maintains, and updates the GO knowledgebase. The GO knowledgebase consists of three components: (1) the GO - a computational knowledge structure describing the functional characteristics of genes; (2) GO annotations - evidence-supported statements asserting that a specific gene product has a particular functional characteristic; and (3) GO Causal Activity Models (GO-CAMs) - mechanistic models of molecular "pathways"(GO biological processes) created by linking multiple GO annotations using defined relations. Each of these components is continually expanded, revised, and updated in response to newly published discoveries and receives extensive QA checks, reviews, and user feedback. For each of these components, we provide a description of the current contents, recent developments to keep the knowledgebase up to date with new discoveries, and guidance on how users can best make use of the data that we provide. We conclude with future directions for the project. © 2023 The Author(s). Published by Oxford University Press on behalf of The Genetics Society of America.},

note = {Cited by: 557; All Open Access, Hybrid Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Leonardi2023202,

title = {Expanding the genetics and phenotypic spectrum of Lysine-specific demethylase 5C (KDM5C): a report of 13 novel variants},

author = { Emanuela Leonardi and Maria Cristina Aspromonte and Denise Drongitis and Elisa Bettella and Lucia Verrillo and Roberta Polli and Meriel McEntagart and Laura Licchetta and Robertino Dilena and Stefano D’Arrigo and Claudia Ciaccio and Silvia Esposito and Vincenzo Leuzzi and Annalaura Torella and Demetrio Baldo and Fortunato Lonardo and Giulia Bonato and Serena Pellegrin and Franco Stanzial and Renata Posmyk and Ewa Kaczorowska and Miryam Carecchio and Monika Gos and Sylwia Rzońca-Niewczas and Maria Giuseppina Miano and Alessandra Murgia},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85142646250&doi=10.1038%2fs41431-022-01233-4&partnerID=40&md5=56692e2c9b3994a0703776134808e698},

doi = {10.1038/s41431-022-01233-4},

issn = {10184813},

year  = {2023},

date = {2023-01-01},

journal = {European Journal of Human Genetics},

volume = {31},

number = {2},

pages = {202 – 215},

publisher = {Springer Nature},

abstract = {Lysine-specific demethylase 5C (KDM5C) has been identified as an important chromatin remodeling gene, contributing to X-linked neurodevelopmental disorders (NDDs). The KDM5C gene, located in the Xp22 chromosomal region, encodes the H3K4me3-me2 eraser involved in neuronal plasticity and dendritic growth. Here we report 30 individuals carrying 13 novel and one previously identified KDM5C variants. Our cohort includes the first reported case of somatic mosaicism in a male carrying a KDM5C nucleotide substitution, and a dual molecular finding in a female carrying a homozygous truncating FUCA1 alteration together with a de novo KDM5C variant. With the use of next generation sequencing strategies, we detected 1 frameshift, 1 stop codon, 2 splice-site and 10 missense variants, which pathogenic role was carefully investigated by a thorough bioinformatic analysis. The pattern of X-chromosome inactivation was found to have an impact on KDM5C phenotypic expression in females of our cohort. The affected individuals of our case series manifested a neurodevelopmental condition characterized by psychomotor delay, intellectual disability with speech disorders, and behavioral features with particular disturbed sleep pattern; other observed clinical manifestations were short stature, obesity and hypertrichosis. Collectively, these findings expand the current knowledge about the pathogenic mechanisms leading to dysfunction of this important chromatin remodeling gene and contribute to a refinement of the KDM5C phenotypic spectrum. © 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.},

note = {Cited by: 5; All Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Quaglia2022D480,

title = {DisProt in 2022: Improved quality and accessibility of protein intrinsic disorder annotation},

author = { Federica Quaglia and Bálint Meszáros and Edoardo Salladini and András Hatos and Rita Pancsa and Lucía B. Chemes and Mátyás Pajkos and Tamas Lazar and Samuel Peña-Díaz and Jaime Santos and Veronika Ács and Nazanin Farahi and Erzsebet Fichó and Maria Cristina Aspromonte and Claudio Bassot and Anastasia Chasapi and Norman E. Davey and Radoslav Davidović and Laszlo Dobson and Arne Elofsson and Gábor Erdos and Pascale Gaudet and Michelle Giglio and Juliana Glavina and Javier Iserte and Valentín Iglesias and Zsófia Kálmán and Matteo Lambrughi and Emanuela Leonardi and Sonia Longhi and Sandra Macedo-Ribeiro and Emiliano Maiani and Julia Marchetti and Cristina Marino-Buslje and Attila Meszáros and Alexander Miguel Monzon and Giovanni Minervini and Suvarna Nadendla and Juliet F. Nilsson and Marian Novotný and Christos A. Ouzounis and Nicolás Palopoli and Elena Papaleo and Pedro Jose Barbosa Pereira and Gabriele Pozzati and Vasilis J. Promponas and Jordi Pujols and Alma Carolina Sanchez Rocha and Martin Salas and Luciana Rodriguez Sawicki and Eva Schad and Aditi Shenoy and Tamás Szaniszló and Konstantinos D. Tsirigos and Nevena Veljkovic and Gustavo Parisi and Salvador Ventura and Zsuzsanna Dosztányi and Peter Tompa and Silvio C. E. Tosatto and Damiano Piovesan},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85125157608&doi=10.1093%2fnar%2fgkab1082&partnerID=40&md5=270bf5618598238b9e614e8070e3723a},

doi = {10.1093/nar/gkab1082},

issn = {03051048},

year  = {2022},

date = {2022-01-01},

journal = {Nucleic Acids Research},

volume = {50},

number = {D1},

pages = {D480 – D487},

publisher = {Oxford University Press},

abstract = {The Database of Intrinsically Disordered Proteins (DisProt, URL: https://disprot.org) is the major repository of manually curated annotations of intrinsically disordered proteins and regions from the literature. We report here recent updates of DisProt version 9, including a restyled web interface, refactored Intrinsically Disordered Proteins Ontology (IDPO), improvements in the curation process and significant content growth of around 30%. Higher quality and consistency of annotations is provided by a newly implemented reviewing process and training of curators. The increased curation capacity is fostered by the integration of DisProt with APICURON, a dedicated resource for the proper attribution and recognition of biocuration efforts. Better interoperability is provided through the adoption of the Minimum Information About Disorder (MIADE) standard, an active collaboration with the Gene Ontology (GO) and Evidence and Conclusion Ontology (ECO) consortia and the support of the ELIXIR infrastructure. © 2022 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.},

note = {Cited by: 110; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cesca2020855,

title = {Frequency of Usher gene mutations in non-syndromic hearing loss: higher variability of the Usher phenotype},

author = { Federica Cesca and Elisa Bettella and Roberta Polli and Emanuela Leonardi and Maria Cristina Aspromonte and Barbara Sicilian and Franco Stanzial and Francesco Benedicenti and Alberto Sensi and Andrea Ciorba and Stefania Bigoni and Elona Cama and Pietro Scimemi and Rosamaria Santarelli and Alessandra Murgia},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85085478685&doi=10.1038%2fs10038-020-0783-1&partnerID=40&md5=14dfffed6f51434ee852e8c1ab314cc6},

doi = {10.1038/s10038-020-0783-1},

issn = {14345161},

year  = {2020},

date = {2020-01-01},

journal = {Journal of Human Genetics},

volume = {65},

number = {10},

pages = {855 – 864},

publisher = {Springer Nature},

abstract = {Non-syndromic hearing loss (NSHL) is characterized by a vast genetic heterogeneity; some syndromic forms as Usher syndrome (USH) have onset as isolated deafness and then evolve later in life. We developed an NGS targeted gene-panel containing 59 genes and a customized bioinformatic pipeline for the analysis of DNA samples from clinically highly selected subjects with sensorineural hearing loss, previously resulted negative for GJB2 mutations/GJB6 deletions. Among the 217 tested subjects, 24 (11.1%) were found to carry mutations in genes involved both in NSHL and USH. For 6 out of 24 patients a diagnosis of USH was performed. Eleven subjects out of 24 had hearing loss without vestibular or ocular dysfunction and, due to their young age, it was not possible to establish whether their phenotype could be NSHL or USH. Seven subjects were diagnosed with NSHL, due to their age and phenotype. A total of 41 likely pathogenic/pathogenic mutations were identified, among which 17 novel ones. We report a high frequency of mutations in genes involved both in NSHL and in USH in a cohort of individuals tested for seemingly isolated deafness. Our data also highlight a wider than expected phenotypic variability in the USH phenotype. © 2020, The Author(s), under exclusive licence to The Japan Society of Human Genetics.},

note = {Cited by: 7},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Leonardi2020,

title = {A novel WAC loss of function mutation in an individual presenting with encephalopathy related to status epilepticus during sleep (ESES)},

author = { Emanuela Leonardi and Mariagrazia Bellini and Maria C. Aspromonte and Roberta Polli and Anna Mercante and Claudia Ciaccio and Elisa Granocchio and Elisa Bettella and Ilaria Donati and Elisa Cainelli and Stefania Boni and Stefano Sartori and Chiara Pantaleoni and Clementina Boniver and Alessandra Murgia},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85082481693&doi=10.3390%2fgenes11030344&partnerID=40&md5=e698d9eb8008cf9749e41d6bc1e55939},

doi = {10.3390/genes11030344},

issn = {20734425},

year  = {2020},

date = {2020-01-01},

journal = {Genes},

volume = {11},

number = {3},

publisher = {MDPI AG},

abstract = {WAC (WW Domain Containing Adaptor With Coiled-Coil) mutations have been reported in only 20 individuals presenting a neurodevelopmental disorder characterized by intellectual disability, neonatal hypotonia, behavioral problems, and mildly dysmorphic features. Using targeted deep sequencing, we screened a cohort of 630 individuals with variable degrees of intellectual disability and identified five WAC rare variants: two variants were inherited from healthy parents; two previously reported de novo mutations, c.1661_1664del (p.Ser554*) and c.374C>A (p.Ser125*); and a novel c.381+2T>C variant causing the skipping of exon 4 of the gene, inherited from a reportedly asymptomatic father with somatic mosaicism. A phenotypic evaluation of this individual evidenced areas of cognitive and behavioral deficits. The patient carrying the novel splicing mutation had a clinical history of encephalopathy related to status epilepticus during slow sleep (ESES), recently reported in another WAC individual. This first report of a WAC somatic mosaic remarks the contribution of mosaicism in the etiology of neurodevelopmental and neuropsychiatric disorders. We summarized the clinical data of reported individuals with WAC pathogenic mutations, which together with our findings, allowed for the expansion of the phenotypic spectrum of WAC-related disorders. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.},

note = {Cited by: 13; All Open Access, Gold Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Carraro20191330,

title = {Assessment of patient clinical descriptions and pathogenic variants from gene panel sequences in the CAGI-5 intellectual disability challenge},

author = { Marco Carraro and Alexander Miguel Monzon and Luigi Chiricosta and Francesco Reggiani and Maria Cristina Aspromonte and Mariagrazia Bellini and Kymberleigh Pagel and Yuxiang Jiang and Predrag Radivojac and Kunal Kundu and Lipika R. Pal and Yizhou Yin and Ivan Limongelli and Gaia Andreoletti and John Moult and Stephen J. Wilson and Panagiotis Katsonis and Olivier Lichtarge and Jingqi Chen and Yaqiong Wang and Zhiqiang Hu and Steven E. Brenner and Carlo Ferrari and Alessandra Murgia and Silvio C.E. Tosatto and Emanuela Leonardi},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85068522592&doi=10.1002%2fhumu.23823&partnerID=40&md5=95226586e1b2af0acd7bd52b55953325},

doi = {10.1002/humu.23823},

issn = {10597794},

year  = {2019},

date = {2019-01-01},

journal = {Human Mutation},

volume = {40},

number = {9},

pages = {1330 – 1345},

publisher = {John Wiley and Sons Inc.},

abstract = {The Critical Assessment of Genome Interpretation-5 intellectual disability challenge asked to use computational methods to predict patient clinical phenotypes and the causal variant(s) based on an analysis of their gene panel sequence data. Sequence data for 74 genes associated with intellectual disability (ID) and/or autism spectrum disorders (ASD) from a cohort of 150 patients with a range of neurodevelopmental manifestations (i.e. ID, autism, epilepsy, microcephaly, macrocephaly, hypotonia, ataxia) have been made available for this challenge. For each patient, predictors had to report the causative variants and which of the seven phenotypes were present. Since neurodevelopmental disorders are characterized by strong comorbidity, tested individuals often present more than one pathological condition. Considering the overall clinical manifestation of each patient, the correct phenotype has been predicted by at least one group for 93 individuals (62%). ID and ASD were the best predicted among the seven phenotypic traits. Also, causative or potentially pathogenic variants were predicted correctly by at least one group. However, the prediction of the correct causative variant seems to be insufficient to predict the correct phenotype. In some cases, the correct prediction has been supported by rare or common variants in genes different from the causative one. © 2019 Wiley Periodicals, Inc.},

note = {Cited by: 10; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}