@article{SCOPUS_ID:85131795908,

title = {Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome},

author = {Margot A. Cousin and Emma L. Veale and Nikita R. Dsouza and Swarnendu Tripathi and Robyn G. Holden and Maria Arelin and Geoffrey Beek and Mir Reza Bekheirnia and Jasmin Beygo and Vikas Bhambhani and Martin Bialer and Stefania Bigoni and Cyrus Boelman and Jenny Carmichael and Thomas Courtin and Benjamin Cogne and Ivana Dabaj and Diane Doummar and Laura Fazilleau and Alessandra Ferlini and Ralitza H. Gavrilova and John M. Graham and Tobias B. Haack and Jane Juusola and Sarina G. Kant and Saima Kayani and Boris Keren and Petra Ketteler and Chiara Klöckner and Tamara T. Koopmann and Teresa M. Kruisselbrink and Alma Kuechler and Laëtitia Lambert and Xénia Latypova and Robert Roger Lebel and Magalie S. Leduc and Emanuela Leonardi and Andrea M. Lewis and Wendy Liew and Keren Machol and Samir Mardini and Kirsty McWalter and Cyril Mignot and Julie McLaughlin and Alessandra Murgia and Vinodh Narayanan and Caroline Nava and Sonja Neuser and Mathilde Nizon and Davide Ognibene and Joohyun Park and Konrad Platzer and Céline Poirsier and Maximilian Radtke and Keri Ramsey and Cassandra K. Runke and Maria J. Guillen Sacoto and Fernando Scaglia and Marwan Shinawi and Stephanie Spranger and Ee Shien Tan and John Taylor and Anne-Sophie Trentesaux and Filippo Vairo and Rebecca Willaert and Neda Zadeh and Raul Urrutia and Dusica Babovic-Vuksanovic and Michael T. Zimmermann and Alistair Mathie and Eric W. Klee},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85131795908&origin=inward},

doi = {10.1186/s13073-022-01064-4},

year  = {2022},

date = {2022-01-01},

journal = {Genome Medicine},

volume = {14},

number = {1},

publisher = {BioMed Central Ltd},

abstract = {© 2022, The Author(s).Background: Genomics enables individualized diagnosis and treatment, but large challenges remain to functionally interpret rare variants. To date, only one causative variant has been described for KCNK9 imprinting syndrome (KIS). The genotypic and phenotypic spectrum of KIS has yet to be described and the precise mechanism of disease fully understood. Methods: This study discovers mechanisms underlying KCNK9 imprinting syndrome (KIS) by describing 15 novel KCNK9 alterations from 47 KIS-affected individuals. We use clinical genetics and computer-assisted facial phenotyping to describe the phenotypic spectrum of KIS. We then interrogate the functional effects of the variants in the encoded TASK3 channel using sequence-based analysis, 3D molecular mechanic and dynamic protein modeling, and in vitro electrophysiological and functional methodologies. Results: We describe the broader genetic and phenotypic variability for KIS in a cohort of individuals identifying an additional mutational hotspot at p.Arg131 and demonstrating the common features of this neurodevelopmental disorder to include motor and speech delay, intellectual disability, early feeding difficulties, muscular hypotonia, behavioral abnormalities, and dysmorphic features. The computational protein modeling and in vitro electrophysiological studies discover variability of the impact of KCNK9 variants on TASK3 channel function identifying variants causing gain and others causing loss of conductance. The most consistent functional impact of KCNK9 genetic variants, however, was altered channel regulation. Conclusions: This study extends our understanding of KIS mechanisms demonstrating its complex etiology including gain and loss of channel function and consistent loss of channel regulation. These data are rapidly applicable to diagnostic strategies, as KIS is not identifiable from clinical features alone and thus should be molecularly diagnosed. Furthermore, our data suggests unique therapeutic strategies may be needed to address the specific functional consequences of KCNK9 variation on channel function and regulation.},

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

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85122738953,

title = {Feasibility of Screening for Chromosome 15 Imprinting Disorders in 16579 Newborns by Using a Novel Genomic Workflow},

author = {David E. Godler and Ling Ling and Dinusha Gamage and Emma K. Baker and Minh Bui and Michael J. Field and Carolyn Rogers and Merlin G. Butler and Alessandra Murgia and Emanuela Leonardi and Roberta Polli and Charles E. Schwartz and Cindy D. Skinner and Angelica M. Alliende and Lorena Santa Maria and James Pitt and Ronda Greaves and David Francis and Ralph Oertel and Min Wang and Cas Simons and David J. Amor},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85122738953&origin=inward},

doi = {10.1001/jamanetworkopen.2021.41911},

year  = {2022},

date = {2022-01-01},

journal = {JAMA Network Open},

volume = {5},

number = {1},

publisher = {American Medical Association},

abstract = {© 2022 American Medical Association. All rights reserved.Importance: Newborn screening for Angelman syndrome (AS), Prader-Willi syndrome (PWS), and chromosome 15 duplication syndrome (Dup15q) may lead to benefit from early diagnosis and treatment. Objective: To examine the feasibility of newborn screening for these chromosome 15 imprinting disorders at population scale. Design, Setting, and Participants: In this diagnostic study, the validation data set for the first-tier SNRPN test, called methylation-specific quantitative melt analysis (MS-QMA), included 109 PWS, 48 AS, 9 Dup15q, and 1190 population control newborn blood spots (NBS) and peripheral tissue samples from participants recruited from January 2000 to December 2016. The test data set included NBS samples from 16579 infants born in 2011. Infants with an NBS identified as positive for PWS, AS, or Dup15q by the first-tier test were referred for droplet digital polymerase chain reaction, real-time polymerase chain reaction, and low-coverage whole-genome sequencing for confirmatory testing. Data analyses were conducted between February 12, 2015, and August 15, 2020. Results: In the validation data set, the median age for the 77 patients with PWS was 3.00 years (IQR, 0.01-44.50 years); for the 46 patients with AS, 2.76 years (IQR, 0.028 to 49.00 years); and for the 9 patients with Dup15q, 4.00 years (IQR, 1.00 to 28.00 years). Thirty-eight patients (51.4%) in the PWS group, 20 patients (45.5%) in the AS group, and 6 patients (66.7%) in the Dup15q group who had sex reported were male. The validation data set showed MS-QMA sensitivity of 99.0% for PWS, 93.8% for AS, and 77.8% for Dup15q; specificity of 100% for PWS, AS, and Dup15q; positive predictive and negative predictive values of 100% for PWS and AS; and a positive predictive value of 87.5% and negative predictive value of 100% for Dup15q. In the test data set of NBS samples from 16579 infants, 92 had a positive test result using a methylation ratio cut-off of 3 standard deviations from the mean. Of these patients, 2 were confirmed to have PWS; 2, AS; and 1, maternal Dup15q. With the use of more conservative PWS- and AS-specific thresholds for positive calls from the validation data set, 9 positive NBS results were identified by MS-QMA in this cohort. The 2 PWS and 2 AS calls were confirmed by second-tier testing, but the 1 Dup15q case was not confirmed. Together, these results provided prevalence estimates of 1 in 8290 for both AS and PWS and 1 in 16579 for maternal Dup15q, with positive predictive values for first-tier testing at 67.0% for AS, 33.0% for PWS, and 44.0% for combined detection of chromosome 15 imprinting disorders for the validation data set. Conclusions and Relevance: The findings of this diagnostic study suggest that it is feasible to screen for all chromosome 15 imprinting disorders using SNRPN methylation analysis, with 5 individuals identified with these disorders out of 16579 infants screened..},

note = {Cited by: 24; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85125157608,

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/record/display.uri?eid=2-s2.0-85125157608&origin=inward},

doi = {10.1093/nar/gkab1082},

year  = {2022},

date = {2022-01-01},

journal = {Nucleic Acids Research},

volume = {50},

number = {D1},

pages = {D480-D487},

publisher = {Oxford University Press},

abstract = {© 2022 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.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.},

note = {Cited by: 125; Open Access},

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}

}

@article{SCOPUS_ID:85104988931,

title = {Critical assessment of protein intrinsic disorder prediction},

author = {Marco Necci and Damiano Piovesan and Md Tamjidul Hoque and Ian Walsh and Sumaiya Iqbal and Michele Vendruscolo and Pietro Sormanni and Chen Wang and Daniele Raimondi and Ronesh Sharma and Yaoqi Zhou and Thomas Litfin and Oxana Valerianovna Galzitskaya and Michail Yu. Lobanov and Wim Vranken and Björn Wallner and Claudio Mirabello and Nawar Malhis and Zsuzsanna Dosztányi and Gábor Erdős and Bálint Mészáros and Jianzhao Gao and Kui Wang and Gang Hu and Zhonghua Wu and Alok Sharma and Jack Hanson and Kuldip Paliwal and Isabelle Callebaut and Tristan Bitard-Feildel and Gabriele Orlando and Zhenling Peng and Jinbo Xu and Sheng Wang and David T. Jones and Domenico Cozzetto and Fanchi Meng and Jing Yan and Jörg Gsponer and Jianlin Cheng and Tianqi Wu and Lukasz Kurgan and Vasilis J. Promponas and Stella Tamana and Cristina Marino-Buslje and Elizabeth Martínez-Pérez and Anastasia Chasapi and Christos Ouzounis and A. Keith Dunker and Andrey V. Kajava and Jeremy Y. Leclercq and Burcu Aykac-Fas and Matteo Lambrughi and Emiliano Maiani and Elena Papaleo and Lucia Beatriz Chemes and Lucía Álvarez and Nicolás S. González-Foutel and Valentin Iglesias and Jordi Pujols and Salvador Ventura and Nicolás Palopoli and Guillermo Ignacio Benítez and Gustavo Parisi and Claudio Bassot and Arne Elofsson and Sudha Govindarajan and John Lamb and Marco Salvatore and András Hatos and Alexander Miguel Monzon and Martina Bevilacqua and Ivan Mičetić and Giovanni Minervini and Lisanna Paladin and Federica Quaglia and Emanuela Leonardi and Norman Davey and Tamas Horvath and Orsolya Panna Kovacs and Nikoletta Murvai and Rita Pancsa and Eva Schad and Beata Szabo and Agnes Tantos and Sandra Macedo-Ribeiro and Jose Antonio Manso and Pedro José Barbosa Pereira and Radoslav Davidović and Nevena Veljkovic and Borbála Hajdu-Soltész and Mátyás Pajkos and Tamás Szaniszló and Mainak Guharoy and Tamas Lazar and Mauricio Macossay-Castillo and Peter Tompa and Silvio C. E. Tosatto},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85104988931&origin=inward},

doi = {10.1038/s41592-021-01117-3},

year  = {2021},

date = {2021-01-01},

journal = {Nature Methods},

volume = {18},

number = {5},

pages = {472-481},

publisher = {Nature Research},

abstract = {© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.Intrinsically disordered proteins, defying the traditional protein structure–function paradigm, are a challenge to study experimentally. Because a large part of our knowledge rests on computational predictions, it is crucial that their accuracy is high. The Critical Assessment of protein Intrinsic Disorder prediction (CAID) experiment was established as a community-based blind test to determine the state of the art in prediction of intrinsically disordered regions and the subset of residues involved in binding. A total of 43 methods were evaluated on a dataset of 646 proteins from DisProt. The best methods use deep learning techniques and notably outperform physicochemical methods. The top disorder predictor has Fmax = 0.483 on the full dataset and Fmax = 0.792 following filtering out of bona fide structured regions. Disordered binding regions remain hard to predict, with Fmax = 0.231. Interestingly, computing times among methods can vary by up to four orders of magnitude.},

note = {Cited by: 233; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85104381200,

title = {A Missense de Novo Variant in the CASK -interactor KIRREL3 Gene Leading to Neurodevelopmental Disorder with Mild Cerebellar Hypoplasia},

author = {Claudia Ciaccio and Emanuela Leonardi and Roberta Polli and Alessandra Murgia and Stefano D'Arrigo and Elisa Granocchio and Luisa Chiapparini and Chiara Pantaleoni and Silvia Esposito},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85104381200&origin=inward},

doi = {10.1055/s-0041-1725964},

year  = {2021},

date = {2021-01-01},

journal = {Neuropediatrics},

volume = {52},

number = {6},

pages = {484-488},

publisher = {Georg Thieme Verlag},

abstract = {© 2021 Georg Thieme Verlag. All rights reserved.KIRREL3 is a gene important for the central nervous system development-in particular for the process of neuronal migration, axonal fasciculation, and synaptogenesis-and colocalizes and cooperates in neurons with CASK gene. Alterations of KIRREL3 have been linked to neurodevelopmental disorders, ranging from developmental delay, to autism spectrum disorder, to attention deficit/hyperactivity disorder. The underlying mechanism is not yet fully understood, as it has been hypothesized a fully dominant effect, a risk factor role of KIRREL3 partially penetrating variants, and a recessive inheritance pattern. We report a novel and de novo KIRREL3 mutation in a child affected by severe neurodevelopmental disorder and with brain magnetic resonance imaging evidence of mega cisterna magna and mild cerebellar hypoplasia. This case strengthens the hypothesis that dominant KIRREL3 variants may lead to neurodevelopmental disruption; furthermore, given the strong interaction between KIRREL3 and CASK, we discuss as posterior fossa anomalies may also be part of the phenotype of KIRREL3 -related syndrome.},

note = {Cited by: 5},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@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: 16; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85077666918,

title = {DisProt: Intrinsic protein disorder annotation in 2020},

author = {András Hatos and Borbála Hajdu-Soltész and Alexander M. Monzon and Nicolas Palopoli and Lucía Álvarez and Burcu Aykac-Fas and Claudio Bassot and Guillermo I. Benítez and Martina Bevilacqua and Anastasia Chasapi and Lucia Chemes and Norman E. Davey and Radoslav Davidović and A Keith Dunker and Arne Elofsson and Julien Gobeill and Nicolás S González Foutel and Govindarajan Sudha and Mainak Guharoy and Tamas Horvath and Valentin Iglesias and Andrey V. Kajava and Orsolya P. Kovacs and John Lamb and Matteo Lambrughi and Tamas Lazar and Jeremy Y. Leclercq and Emanuela Leonardi and Sandra MacEdo-Ribeiro and Mauricio MacOssay-Castillo and Emiliano Maiani and José A. Manso and Cristina Marino-Buslje and Elizabeth Martínez-Pérez and Bálint Mészáros and Ivan Mičetić and Giovanni Minervini and Nikoletta Murvai and Marco Necci and Christos A. Ouzounis and Mátyás Pajkos and Lisanna Paladin and Rita Pancsa and Elena Papaleo and Gustavo Parisi and Emilie Pasche and Pedro J. Barbosa Pereira and Vasilis J. Promponas and Jordi Pujols and Federica Quaglia and Patrick Ruch and Marco Salvatore and Eva Schad and Beata Szabo and Tamás Szaniszló and Stella Tamana and Agnes Tantos and Nevena Veljkovic and Salvador Ventura and Wim Vranken and Zsuzsanna Dosztányi and Peter Tompa and Silvio C. E. Tosatto and Damiano Piovesan},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85077666918&origin=inward},

doi = {10.1093/nar/gkz975},

year  = {2020},

date = {2020-01-01},

journal = {Nucleic Acids Research},

volume = {48},

number = {D1},

pages = {D269-D276},

publisher = {Oxford University Press},

abstract = {© 2019 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.The Database of Protein Disorder (DisProt, URL: https://disprot.org) provides manually curated annotations of intrinsically disordered proteins from the literature. Here we report recent developments with DisProt (version 8), including the doubling of protein entries, a new disorder ontology, improvements of the annotation format and a completely new website. The website includes a redesigned graphical interface, a better search engine, a clearer API for programmatic access and a new annotation interface that integrates text mining technologies. The new entry format provides a greater flexibility, simplifies maintenance and allows the capture of more information from the literature. The new disorder ontology has been formalized and made interoperable by adopting the OWL format, as well as its structure and term definitions have been improved. The new annotation interface has made the curation process faster and more effective. We recently showed that new DisProt annotations can be effectively used to train and validate disorder predictors. We believe the growth of DisProt will accelerate, contributing to the improvement of function and disorder predictors and therefore to illuminate the 'dark' proteome.},

note = {Cited by: 206; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85099166712,

title = {Expanding the genetic landscape of Rett syndrome to include lysine acetyltransferase 6A (KAT6A)},

author = {Simranpreet Kaur and Nicole J. Van Bergen and Bruria Ben-Zeev and Emanuela Leonardi and Tiong Y. Tan and David Coman and Benjamin Kamien and Susan M. White and Miya St John and Dean Phelan and Kristin Rigbye and Sze Chern Lim and Michelle C. Torres and Melanie Marty and Elena Savva and Teresa Zhao and Sean Massey and Alessandra Murgia and Wendy A. Gold and John Christodoulou},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85099166712&origin=inward},

doi = {10.1016/j.jgg.2020.09.003},

year  = {2020},

date = {2020-01-01},

journal = {Journal of Genetics and Genomics},

volume = {47},

number = {10},

pages = {650-654},

publisher = {Institute of Genetics and Developmental Biology},

note = {Cited by: 2},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:85085478685,

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/record/display.uri?eid=2-s2.0-85085478685&origin=inward},

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

year  = {2020},

date = {2020-01-01},

journal = {Journal of Human Genetics},

volume = {65},

number = {10},

pages = {855-864},

publisher = {Springer Nature},

abstract = {© 2020, The Author(s), under exclusive licence to The Japan Society of Human Genetics.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.},

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

keywords = {},

pubstate = {published},

tppubtype = {article}

}