{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T19:22:06Z","timestamp":1775503326692,"version":"3.50.1"},"reference-count":15,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T00:00:00Z","timestamp":1631145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["\u201cRicerca Corrente 2018-2021\u201d"],"award-info":[{"award-number":["\u201cRicerca Corrente 2018-2021\u201d"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Audiology Research"],"abstract":"<jats:p>Hearing loss (HL) affects 1\u20133 newborns per 1000 and, in industrialized countries, recognizes a genetic etiology in more than 80% of the congenital cases. Excluding GJB2 and GJB6, OTOA is one of the leading genes associated with autosomal recessive non-syndromic HL. Allelic heterogeneity linked to OTOA also includes genomic rearrangements facilitated by non-allelic homologous recombination with the neighboring OTOAP1 pseudogene. We present a couple of Italian siblings affected by moderate to severe sensorineural hearing loss (SNHL) due to compound heterozygosity at the OTOA locus. Multigene panel next-generation sequencing identified the c.2223G&gt;A, p.(Trp741*) variant transmitted from the unaffected mother. Assuming the existence of a second paternal deleterious variant which evaded detection at sequencing, genomic array analysis found a ~150 Kb microdeletion of paternal origin and spanning part of OTOA. Both deleterious alleles were identified for the first time. This study demonstrates the utility of an integrated approach to solve complex cases and allow appropriate management to affected individuals and at-risk relatives.<\/jats:p>","DOI":"10.3390\/audiolres11030041","type":"journal-article","created":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T12:20:37Z","timestamp":1631190037000},"page":"443-451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Compound Heterozygosity for OTOA Truncating Variant and Genomic Rearrangement Cause Autosomal Recessive Sensorineural Hearing Loss in an Italian Family"],"prefix":"10.3390","volume":"11","author":[{"given":"Rocco Pio","family":"Ortore","sequence":"first","affiliation":[{"name":"Division of Maxillofacial Surgery and Otolaryngology, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Pia","family":"Leone","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orazio","family":"Palumbo","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Petracca","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6490-1746","authenticated-orcid":false,"given":"Eleonora M. C.","family":"Trecca","sequence":"additional","affiliation":[{"name":"Division of Maxillofacial Surgery and Otolaryngology, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aurelio","family":"D\u2019Ecclesia","sequence":"additional","affiliation":[{"name":"Division of Maxillofacial Surgery and Otolaryngology, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ciro Lucio","family":"Vigliaroli","sequence":"additional","affiliation":[{"name":"Division of Maxillofacial Surgery and Otolaryngology, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3604-194X","authenticated-orcid":false,"given":"Lucia","family":"Micale","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7605-2953","authenticated-orcid":false,"given":"Francesco","family":"Longo","sequence":"additional","affiliation":[{"name":"Division of Maxillofacial Surgery and Otolaryngology, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Melchionda","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Castori","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1056\/NEJMra050700","article-title":"Newborn hearing screening\u2014A silent revolution","volume":"354","author":"Morton","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1097\/MOP.0b013e3283588f5e","article-title":"Genetics: Advances in genetic testing for deafness","volume":"24","author":"Shearer","year":"2012","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_3","first-page":"117","article-title":"Non-syndromic hearing loss: Clinical and diagnostic challenges","volume":"32","author":"Vona","year":"2020","journal-title":"Med. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1136\/archdischild-2014-306099","article-title":"Genetic investigations in childhood deafness","volume":"100","author":"Parker","year":"2015","journal-title":"Arch. Dis. Child."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1097\/00125817-200207000-00004","article-title":"GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: A HuGE review","volume":"4","author":"Kenneson","year":"2002","journal-title":"Genet. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6240","DOI":"10.1073\/pnas.082515999","article-title":"Otoancorin, an inner ear protein restricted to the interface between the apical surface of sensory epithelia and their overlying acellular gels, is defective in autosomal recessive deafness DFNB22","volume":"99","author":"Zwaenepoel","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1002\/humu.23630","article-title":"ClinGen Hearing Loss Clinical Domain Working Group. Expert specification of the ACMG\/AMP variant interpretation guidelines for genetic hearing loss","volume":"39","author":"Oza","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Palumbo, O., Palumbo, P., Di Muro, E., Cinque, L., Petracca, A., Carella, M., and Castori, M. (2020). A Private 16q24.2q24.3 Microduplication in a Boy with Intellectual Disability, Speech Delay and Mild Dysmorphic Features. Genes, 11.","DOI":"10.3390\/genes11060707"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1097\/GIM.0b013e3182217a3a","article-title":"Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants","volume":"13","author":"Kearney","year":"2011","journal-title":"Genet. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41436-019-0686-8","article-title":"Technical standards for the interpretation and reporting of constitutional copy-number variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen)","volume":"22","author":"Riggs","year":"2020","journal-title":"Genet. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1101\/gad.1566807","article-title":"Quality control of eukaryotic mRNA: Safeguarding cells from abnormal mRNA function","volume":"21","author":"Isken","year":"2007","journal-title":"Genes Dev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/humu.24167","article-title":"Molecular characterization of pathogenic OTOA gene conversions in hearing loss patients","volume":"42","author":"Laurent","year":"2021","journal-title":"Hum. Mutat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1146\/annurev.genom.9.081307.164217","article-title":"Copy number variation in human health, disease, and evolution","volume":"10","author":"Zhang","year":"2009","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"D986","DOI":"10.1093\/nar\/gkt958","article-title":"The Database of Genomic Variants: A curated collection of structural variation in the human genome","volume":"42","author":"MacDonald","year":"2014","journal-title":"Nucleic Acids Res."}],"container-title":["Audiology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2039-4349\/11\/3\/41\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:59:13Z","timestamp":1760165953000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2039-4349\/11\/3\/41"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,9]]},"references-count":15,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["audiolres11030041"],"URL":"https:\/\/doi.org\/10.3390\/audiolres11030041","relation":{},"ISSN":["2039-4349"],"issn-type":[{"value":"2039-4349","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,9]]}}}