@article{SCOPUS_ID:85191992890,

title = {Expanding the clinical phenotype of SHANK2-related disorders: childhood apraxia of speech in a patient with a novel SHANK2 pathogenic variant},

author = {Elisa Granocchio and Luca Andreoli and Santina Magazù and Daniela Sarti and Emanuela Leonardi and Alessandra Murgia and Claudia Ciaccio},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85191992890&origin=inward},

doi = {10.1007/s00787-024-02452-4},

year  = {2025},

date = {2025-01-01},

journal = {European Child and Adolescent Psychiatry},

volume = {34},

number = {2},

pages = {815-817},

publisher = {Springer Science and Business Media Deutschland GmbH},

note = {Cited by: 1},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85217180047,

title = {CAGI6 ID panel challenge: assessment of phenotype and variant predictions in 415 children with neurodevelopmental disorders (NDDs)},

author = {Maria Cristina Aspromonte and Alessio Del Conte and Shaowen Zhu and Wuwei Tan and Yang Shen and Yexian Zhang and Qi Li and Maggie Haitian Wang and Giulia Babbi and Samuele Bovo and Pier Luigi Martelli and Rita Casadio and Azza Althagafi and Sumyyah Toonsi and Maxat Kulmanov and Robert Hoehndorf and Panagiotis Katsonis and Amanda Williams and Olivier Lichtarge and Su Xian and Wesley Surento and Vikas Pejaver and Sean D. Mooney and Uma Sunderam and Rajgopal Srinivasan and Alessandra Murgia and Damiano Piovesan and Silvio C. E. Tosatto and Emanuela Leonardi},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85217180047&origin=inward},

doi = {10.1007/s00439-024-02722-w},

year  = {2025},

date = {2025-01-01},

journal = {Human Genetics},

publisher = {Springer Science and Business Media Deutschland GmbH},

abstract = {© The Author(s) 2025.The Genetics of Neurodevelopmental Disorders Lab in Padua provided a new intellectual disability (ID) Panel challenge for computational methods to predict patient phenotypes and their causal variants in the context of the Critical Assessment of the Genome Interpretation, 6th edition (CAGI6). Eight research teams submitted a total of 30 models to predict phenotypes based on the sequences of 74 genes (VCF format) in 415 pediatric patients affected by Neurodevelopmental Disorders (NDDs). NDDs are clinically and genetically heterogeneous conditions, with onset in infant age. Here, we assess the ability and accuracy of computational methods to predict comorbid phenotypes based on clinical features described in each patient and their causal variants. We also evaluated predictions for possible genetic causes in patients without a clear genetic diagnosis. Like the previous ID Panel challenge in CAGI5, seven clinical features (ID, ASD, ataxia, epilepsy, microcephaly, macrocephaly, hypotonia), and variants (Pathogenic/Likely Pathogenic, Variants of Uncertain Significance and Risk Factors) were provided. The phenotypic traits and variant data of 150 patients from the CAGI5 ID Panel Challenge were provided as training set for predictors. The CAGI6 challenge confirms CAGI5 results that predicting phenotypes from gene panel data is highly challenging, with AUC values close to random, and no method able to predict relevant variants with both high accuracy and precision. However, a significant improvement is noted for the best method, with recall increasing from 66% to 82%. Several groups also successfully predicted difficult-to-detect variants, emphasizing the importance of variants initially excluded by the Padua NDD Lab.},

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

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:86000084600,

title = {Genetic variants and phenotypic data curated for the CAGI6 intellectual disability panel challenge},

author = {Maria Cristina Aspromonte and Alessio Del Conte and Roberta Polli and Demetrio Baldo and Francesco Benedicenti and Elisa Bettella and Stefania Bigoni and Stefania Boni and Claudia Ciaccio and Stefano D’Arrigo and Ilaria Donati and Elisa Granocchio and Isabella Mammi and Donatella Milani and Susanna Negrin and Margherita Nosadini and Fiorenza Soli and Franco Stanzial and Licia Turolla and Damiano Piovesan and Silvio C. E. Tosatto and Alessandra Murgia and Emanuela Leonardi},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-86000084600&origin=inward},

doi = {10.1007/s00439-025-02733-1},

year  = {2025},

date = {2025-01-01},

journal = {Human Genetics},

publisher = {Springer Science and Business Media Deutschland GmbH},

abstract = {© The Author(s) 2025.Neurodevelopmental disorders (NDDs) are common conditions including clinically diverse and genetically heterogeneous diseases, such as intellectual disability, autism spectrum disorders, and epilepsy. The intricate genetic underpinnings of NDDs pose a formidable challenge, given their multifaceted genetic architecture and heterogeneous clinical presentations. This work delves into the intricate interplay between genetic variants and phenotypic manifestations in neurodevelopmental disorders, presenting a dataset curated for the Critical Assessment of Genome Interpretation (CAGI6) ID Panel Challenge. The CAGI6 competition serves as a platform for evaluating the efficacy of computational methods in predicting phenotypic outcomes from genetic data. In this study, a targeted gene panel sequencing has been used to investigate the genetic causes of NDDs in a cohort of 415 paediatric patients. We identified 60 pathogenic and 49 likely pathogenic variants in 102 individuals that accounted for 25% of NDD cases in the cohort. The most mutated genes were ANKRD11, MECP2, ARID1B, ASH1L, CHD8, KDM5C, MED12 and PTCHD1 The majority of pathogenic variants were de novo, with some inherited from mildly affected parents. Loss-of-function variants were the most common type of pathogenic variant. In silico analysis tools were used to assess the potential impact of variants on splicing and structural/functional effects of missense variants. The study highlights the challenges in variant interpretation especially in cases with atypical phenotypic manifestations. Overall, this study provides valuable insights into the genetic causes of NDDs and emphasises the importance of understanding the underlying genetic factors for accurate diagnosis, and intervention development in neurodevelopmental conditions.},

note = {Cited by: 0; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85176208048,

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/record/display.uri?eid=2-s2.0-85176208048&origin=inward},

doi = {10.1093/nar/gkad928},

year  = {2024},

date = {2024-01-01},

journal = {Nucleic Acids Research},

volume = {52},

number = {D1},

pages = {D434-D441},

publisher = {Oxford University Press},

abstract = {© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.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.},

note = {Cited by: 38; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85188297172,

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/record/display.uri?eid=2-s2.0-85188297172&origin=inward},

doi = {10.1093/database/baae009},

year  = {2024},

date = {2024-01-01},

journal = {Database},

volume = {2024},

publisher = {Oxford University Press},

abstract = {© The Author(s) 2024. Published by Oxford University Press.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.},

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

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85181761325,

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/record/display.uri?eid=2-s2.0-85181761325&origin=inward},

doi = {10.1093/nar/gkad947},

year  = {2024},

date = {2024-01-01},

journal = {Nucleic Acids Research},

volume = {52},

number = {D1},

pages = {D536-D544},

publisher = {Oxford University Press},

abstract = {© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.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.},

note = {Cited by: 19; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85159733545,

title = {CERT1 mutations perturb human development by disrupting sphingolipid homeostasis},

author = {Charlotte Gehin and Museer A. Lone and Winston Lee and Laura Capolupo and Sylvia Ho and Adekemi M. Adeyemi and Erica H. Gerkes and Alexander P. A. Stegmann and Estrella López-Martín and Eva Bermejo-Sánchez and Beatriz Martínez-Delgado and Christiane Zweier and Cornelia Kraus and Bernt Popp and Vincent Strehlow and Daniel Gräfe and Ina Knerr and Eppie R. Jones and Stefano Zamuner and Luciano A. Abriata and Vidya Kunnathully and Brandon E. Moeller and Anthony Vocat and Samuel Rommelaere and Jean-Philippe Bocquete and Evelyne Ruchti and Greta Limoni and Marine Van Campenhoudt and Samuel Bourgeat and Petra Henklein and Christian Gilissen and Bregje W. Bon and Rolph Pfundt and Marjolein H. Willemsen and Jolanda H. Schieving and Emanuela Leonardi and Fiorenza Soli and Alessandra Murgia and Hui Guo and Qiumeng Zhang and Kun Xia and Christina R. Fagerberg and Christoph P. Beier and Martin J. Larsen and Irene Valenzuela and Paula Fernández-Álvarez and Shiyi Xiong and Robert Śmigiel and Vanesa López-González and Lluís Armengol and Manuela Morleo and Angelo Selicorni and Annalaura Torella and Moira Blyth and Nicola S. Cooper and Valerie Wilson and Renske Oegema and Yvan Herenger and Aurore Garde and Ange-Line Bruel and Frederic Tran Mau-Them and Alexis B. R. Maddocks and Jennifer M. Bain and Musadiq A. Bhat and Gregory Costain and Peter Kannu and Ashish Marwaha and Neena L. Champaigne and Michael J. Friez and Ellen B. Richardson and Vykuntaraju K. Gowda and Varunvenkat M. Srinivasan and Yask Gupta and Tze Y. Lim and Simone Sanna-Cherchi and Bruno Lemaitre and Toshiyuki Yamaji and Kentaro Hanada and John E. Burke and Ana Marjia Jakšić and Brian D. McCabe and Paolo De Los Rios and Thorsten Hornemann and Giovanni D’Angelo and Vincenzo A. Gennarino},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85159733545&origin=inward},

doi = {10.1172/JCI165019},

year  = {2023},

date = {2023-01-01},

journal = {Journal of Clinical Investigation},

volume = {133},

number = {10},

publisher = {American Society for Clinical Investigation},

abstract = {© 2023, Gehin et al.Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which is involved in sphingolipid biosynthesis, are associated with intellectual disability, but the pathogenic mechanism remains obscure. Here, we characterize 31 individuals with de novo missense variants in CERT1. Several variants fall into a previously uncharacterized dimeric helical domain that enables CERT homeostatic inactivation, without which sphingolipid production goes unchecked. The clinical severity reflects the degree to which CERT autoregulation is disrupted, and inhibiting CERT pharmacologically corrects morphological and motor abnormalities in a Drosophila model of the disease, which we call ceramide transporter (CerTra) syndrome. These findings uncover a central role for CERT autoregulation in the control of sphingolipid biosynthetic flux, provide unexpected insight into the structural organization of CERT, and suggest a possible therapeutic approach for patients with CerTra syndrome.},

note = {Cited by: 16; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85142646250,

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/record/display.uri?eid=2-s2.0-85142646250&origin=inward},

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

year  = {2023},

date = {2023-01-01},

journal = {European Journal of Human Genetics},

volume = {31},

number = {2},

pages = {202-215},

publisher = {Springer Nature},

abstract = {© 2022, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.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.},

note = {Cited by: 11; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85160965403,

title = {DNA methylation episignatures are sensitive and specific biomarkers for detection of patients with KAT6A/KAT6B variants},

author = {Niels Vos and Jack Reilly and Mariet W Elting and Philippe M Campeau and David Coman and Zornitza Stark and Tiong Yang Tan and David J Amor and Simran Kaur and Miya Stjohn and Angela T Morgan and Benjamin A Kamien and Chirag Patel and Matthew L Tedder and Giuseppe Merla and Paolo Prontera and Marco Castori and Kai Muru and Felicity Collins and John Christodoulou and Janine Smith and Bruria Ben Zeev and Alessandra Murgia and Emanuela Leonardi and Natacha Esber and Antonio Martinez-Monseny and Didac Casas-Alba and Matthew Wallis and Marcel Mannens and Michael A Levy and Raissa Relator and Marielle Alders and Bekim Sadikovic},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85160965403&origin=inward},

doi = {10.2217/epi-2023-0079},

year  = {2023},

date = {2023-01-01},

journal = {Epigenomics},

volume = {15},

number = {6},

pages = {351-367},

publisher = {Newlands Press Ltd},

abstract = {© 2023 Future Medicine Ltd.Accurate diagnosis for patients living with neurodevelopmental disorders is often met with numerous challenges, related to the ambiguity of findings and lack of specificity in genetic variants leading to pathology. Genome-wide DNA methylation analysis has been used to develop highly sensitive and specific 'episignatures' as biomarkers capable of differentiating and classifying complex neurodevelopmental disorders. In this study we describe distinct episignatures for KAT6A syndrome, caused by pathogenic variants in the lysine acetyltransferase A gene (KAT6A), and for the two neurodevelopmental disorders associated with lysine acetyl transferase B (KAT6B). We demonstrate the ability of our models to differentiate between highly overlapping episignatures, increasing the ability to effectively identify and diagnose these conditions.},

note = {Cited by: 4},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85131521999,

title = {Molecular Effects of Mutations in Human Genetic Diseases},

author = {Emanuela Leonardi and Castrense Savojardo and Giovanni Minervini},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85131521999&origin=inward},

doi = {10.3390/ijms23126408},

year  = {2022},

date = {2022-01-01},

journal = {International Journal of Molecular Sciences},

volume = {23},

number = {12},

publisher = {MDPI},

note = {Cited by: 0; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}