Maria Cristina Aspromonte

@article{SCOPUS_ID:85082481693,

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/record/display.uri?eid=2-s2.0-85082481693&origin=inward},

doi = {10.3390/genes11030344},

year  = {2020},

date = {2020-01-01},

journal = {Genes},

volume = {11},

number = {3},

publisher = {MDPI AGPostfachBaselCH-4005rasetti@mdpi.com},

abstract = {© 2020 by the authors. Licensee MDPI, Basel, Switzerland.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.},

note = {Cited by: 17; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85070077996,

title = {Characterization of intellectual disability and autism comorbidity through gene panel sequencing},

author = {Maria C. Aspromonte and Mariagrazia Bellini and Alessandra Gasparini and Marco Carraro and Elisa Bettella and Roberta Polli and Federica Cesca and Stefania Bigoni and Stefania Boni and Ombretta Carlet and Susanna Negrin and Isabella Mammi and Donatella Milani and Angela Peron and Stefano Sartori and Irene Toldo and Fiorenza Soli and Licia Turolla and Franco Stanzial and Francesco Benedicenti and Cristina Marino-Buslje and Silvio C. E. Tosatto and Alessandra Murgia and Emanuela Leonardi},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85070077996&origin=inward},

doi = {10.1002/humu.23822},

year  = {2019},

date = {2019-01-01},

journal = {Human Mutation},

volume = {40},

number = {9},

pages = {1346-1363},

publisher = {John Wiley and Sons Inc.P.O.Box 18667NewarkNJ 07191-8667},

abstract = {© 2019 Wiley Periodicals, Inc.Intellectual disability (ID) and autism spectrum disorder (ASD) are clinically and genetically heterogeneous diseases. Recent whole exome sequencing studies indicated that genes associated with different neurological diseases are shared across disorders and converge on common functional pathways. Using the Ion Torrent platform, we developed a low-cost next-generation sequencing gene panel that has been transferred into clinical practice, replacing single disease-gene analyses for the early diagnosis of individuals with ID/ASD. The gene panel was designed using an innovative in silico approach based on disease networks and mining data from public resources to score disease-gene associations. We analyzed 150 unrelated individuals with ID and/or ASD and a confident diagnosis has been reached in 26 cases (17%). Likely pathogenic mutations have been identified in another 15 patients, reaching a total diagnostic yield of 27%. Our data also support the pathogenic role of genes recently proposed to be involved in ASD. Although many of the identified variants need further investigation to be considered disease-causing, our results indicate the efficiency of the targeted gene panel on the identification of novel and rare variants in patients with ID and ASD.},

note = {Cited by: 50; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85068522592,

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/record/display.uri?eid=2-s2.0-85068522592&origin=inward},

doi = {10.1002/humu.23823},

year  = {2019},

date = {2019-01-01},

journal = {Human Mutation},

volume = {40},

number = {9},

pages = {1330-1345},

publisher = {John Wiley and Sons Inc},

abstract = {© 2019 Wiley Periodicals, Inc.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.},

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

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85034860326,

title = {CNTNAP2 mutations and autosomal dominant epilepsy with auditory features},

author = {Emanuela Leonardi and Emanuela Dazzo and Maria Cristina Aspromonte and Francesco Tabaro and Stefano Pascarelli and Silvio C. E. Tosatto and Roberto Michelucci and Alessandra Murgia and Carlo Nobile},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85034860326&origin=inward},

doi = {10.1016/j.eplepsyres.2017.11.006},

year  = {2018},

date = {2018-01-01},

journal = {Epilepsy Research},

volume = {139},

pages = {51-53},

publisher = {Elsevier B.V.},

abstract = {© 2017 Elsevier B.V.Autosomal dominant epilepsy with auditory features (ADEAF) is clinically characterized by focal seizures with prominent auditory or aphasic auras and absence of structural brain abnormalities. Mutations in LGI1 and RELN genes account for the disorder in about 50% of ADEAF families. In a recent paper, a heterozygous intragenic deletion in the CNTNAP2 gene has been associated to ADEAF in a single family. We screened 28 ADEAF families for mutations in CNTNAP2 by next generation sequencing and copy number variation analyses and found no likely pathogenic mutations segregating with the disease. CNTNAP2 should be screened in genetically unsolved ADEAF families, but causative mutations are expected to be infrequent in this gene.},

note = {Cited by: 4},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85016112986,

title = {DisProt 7.0: A major update of the database of disordered proteins},

author = {Damiano Piovesan and Francesco Tabaro and Ivan Mičetić and Marco Necci and Federica Quaglia and Christopher J. Oldfield and Maria Cristina Aspromonte and Norman E. Davey and Radoslav Davidović and Zsuzsanna Dosztányi and Arne Elofsson and Alessandra Gasparini and András Hatos and Andrey V. Kajava and Lajos Kalmar and Emanuela Leonardi and Tamas Lazar and Sandra Macedo-Ribeiro and Mauricio Macossay-Castillo and Attila Meszaros and Giovanni Minervini and Nikoletta Murvai and Jordi Pujols and Daniel B. Roche and Edoardo Salladini and Eva Schad and Antoine Schramm and Beata Szabo and Agnes Tantos and Fiorella Tonello and Konstantinos D. Tsirigos and Nevena Veljković and Salvador Ventura and Wim Vranken and Per Warholm and Vladimir N. Uversky and A. Keith Dunker and Sonia Longhi and Peter Tompa and Silvio C. E. Tosatto},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85016112986&origin=inward},

doi = {10.1093/nar/gkw1056},

year  = {2017},

date = {2017-01-01},

journal = {Nucleic Acids Research},

volume = {45},

number = {D1},

pages = {D219-D227},

publisher = {Oxford University Press},

abstract = {© The Author(s) 2016.The Database of Protein Disorder (DisProt, URL: www.disprot.org) has been significantly updated and upgraded since its last major renewal in 2007. The current release holds information on more than 800 entries of IDPs/IDRs, i.e. intrinsically disordered proteins or regions that exist and function without a well-defined three-dimensional structure. We have re-curated previous entries to purge DisProt from conflicting cases, and also upgraded the functional classification scheme to reflect continuous advance in the field in the past 10 years or so. We define IDPs as proteins that are disordered along their entire sequence, i.e. entirely lack structural elements, and IDRs as regions that are at least five consecutive residues without well-defined structure. We base our assessment of disorder strictly on experimental evidence, such as X-ray crystallography and nuclear magnetic resonance (primary techniques) and a broad range of other experimental approaches (secondary techniques). Confident and ambiguous annotations are highlighted separately. DisProt 7.0 presents classified knowledge regarding the experimental characterization and functional annotations of IDPs/IDRs, and is intended to provide an invaluable resource for the research community for a better understanding structural disorder and for developing better computational tools for studying disordered proteins.},

note = {Cited by: 214; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:84953293603,

title = {Downregulation of GABAA Receptor Recycling Mediated by HAP1 Contributes to Neuronal Death in In Vitro Brain Ischemia},

author = {Miranda Mele and Maria Cristina Aspromonte and Carlos B. Duarte},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-84953293603&origin=inward},

doi = {10.1007/s12035-015-9661-9},

year  = {2017},

date = {2017-01-01},

journal = {Molecular Neurobiology},

volume = {54},

number = {1},

pages = {45-57},

publisher = {Humana Press Inc.humana@humanapr.com},

abstract = {© 2016, Springer Science+Business Media New York.Downregulation of GABAergic synaptic transmission contributes to the increase in overall excitatory activity in the ischemic brain. A reduction of GABAA receptor (GABAAR) surface expression partly accounts for this decrease in inhibitory activity, but the mechanisms involved are not fully elucidated. In this work, we investigated the alterations in GABAAR trafficking in cultured rat hippocampal neurons subjected to oxygen/glucose deprivation (OGD), an in vitro model of global brain ischemia, and their impact in neuronal death. The traffic of GABAAR was evaluated after transfection of hippocampal neurons with myc-tagged GABAAR β3 subunits. OGD decreased the rate of GABAAR β3 subunit recycling and reduced the interaction of the receptors with HAP1, a protein involved in the recycling of the receptors. Furthermore, OGD induced a calpain-mediated cleavage of HAP1. Transfection of hippocampal neurons with HAP1A or HAP1B isoforms reduced the OGD-induced decrease in surface expression of GABAAR β3 subunits, and HAP1A maintained the rate of receptor recycling. Furthermore, transfection of hippocampal neurons with HAP1 significantly decreased OGD-induced cell death. These results show a key role for HAP1 protein in the downmodulation of GABAergic neurotransmission during cerebral ischemia, which contributes to neuronal demise.},

note = {Cited by: 24},

keywords = {},

pubstate = {published},

tppubtype = {article}

}