{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T11:19:47Z","timestamp":1740136787007,"version":"3.37.3"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Distinguishing between sporadic and germline\/mosaic NF2-related schwannomatosis is important to ensure that patients have appropriate long-term care. With this report, we describe a unique case of a patient with 4 ipsilateral schwannomas and identify a combination of sequencing modalities that can accurately diagnose mosaic NF2-related schwannomatosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We present a 32-year-old woman with a familial history of vestibular schwannoma in her father and right-sided schwannomas involving the apical and basal turns of cochlea, lateral semicircular canal, and internal auditory canal (IAC). Genetic analysis of blood and frozen tissue from 2 tumors (intralabyrinthine and IAC tumors) was performed using next-generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), and optical genome mapping (OGM).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Germline testing for NF2, LZTR1, and SMARCB1 was negative. Tumor genetic testing revealed a shared NF2 pathogenic variant between the 2 tumors (\u201cfirst hit\u201d) but distinct \u201csecond hit\u201d NF2 variants, including mosaic loss of chromosome 22 in the IAC tumor seen only with OGM, consistent with mosaic NF2-related schwannomatosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Multimodality sequencing, including NGS, MLPA, and OGM, was required to ensure appropriate diagnosis of mosaic NF2-related schwannomatosis in this patient. A similar approach can be used for other patients with multiple ipsilateral tumors and suspected tumor predisposition.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ajcp\/aqae027","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T18:16:09Z","timestamp":1711390569000},"page":"110-114","source":"Crossref","is-referenced-by-count":0,"title":["Four distinct ipsilateral vestibular schwannomas: A case of mosaic <i>NF2<\/i>-related schwannomatosis"],"prefix":"10.1093","volume":"162","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0452-4974","authenticated-orcid":false,"given":"Alexandra E","family":"Tunkel","sequence":"first","affiliation":[{"name":"Division of Otolaryngology\u2013Head and Neck Surgery, The George Washington University School of Medicine & Health Sciences , Washington, DC , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily R","family":"Youner","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head & Neck Surgery, University Hospitals Cleveland Medical Center\/Case Western Reserve School of Medicine, Cleveland , OH , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hayk","family":"Barseghyan","sequence":"additional","affiliation":[{"name":"Center for Genetics Medicine Research, Children\u2019s National Hospital , Washington, DC , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7991-9965","authenticated-orcid":false,"given":"Yulong","family":"Fu","sequence":"additional","affiliation":[{"name":"Division of Genomic Diagnostics and Bioinformatics, Department of Pathology, University of Alabama at Birmingham , Birmingham, AL , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surajit","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Center for Genetics Medicine Research, Children\u2019s National Hospital , Washington, DC , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7595-7726","authenticated-orcid":false,"given":"Miriam","family":"Bornhorst","sequence":"additional","affiliation":[{"name":"Center for Genetics Medicine Research, Children\u2019s National Hospital , Washington, DC , US"},{"name":"Gilbert Neurofibromatosis Institute, Children\u2019s National Hospital , Washington, DC , US"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashkan S","family":"Monfared","sequence":"additional","affiliation":[{"name":"Division of Otolaryngology\u2013Head and Neck Surgery, The George Washington University School of Medicine & Health Sciences , Washington, DC , US"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"2024080105583682000_CIT0001","first-page":"196","article-title":"Intralabyrinthine schwannomas: disease presentation, tumor management, and hearing rehabilitation","volume-title":"J Neurosurg","author":"Choudhury","year":"2019"},{"key":"2024080105583682000_CIT0002","first-page":"60","article-title":"Bilateral intracochlear schwannomas in a patient with no genetic or clinical features of neurofibromatosis type 2","volume-title":"HNO.","author":"Withers","year":"2020"},{"key":"2024080105583682000_CIT0003","first-page":"1241","article-title":"Unilateral double vestibular schwannoma","volume-title":"Oto Neurotol","author":"Kennedy","year":"2005"},{"issue":"1","key":"2024080105583682000_CIT0004","first-page":"34","article-title":"Double localization of a unilateral sporadic vestibular schwannoma","volume":"28","author":"Barbara","year":"2008","journal-title":"Acta Otorhinolaryngol Ital."},{"key":"2024080105583682000_CIT0005","first-page":"e106","article-title":"Multiple unilateral vestibular schwannomas: segmental NF2 or sporadic occurrence","volume-title":"J Neurol Surg Rep","author":"Carlson","year":"2016"},{"key":"2024080105583682000_CIT0006","first-page":"1967","article-title":"Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis: an international consensus recommendation","volume-title":"Genet Med","author":"Plotkin","year":"2022"},{"key":"2024080105583682000_CIT0007","first-page":"540","article-title":"Constitutional LZTR1 mutation presenting with a unilateral vestibular schwannoma in a teenager","volume-title":"Clin Genet.","author":"Gripp","year":"2017"},{"key":"2024080105583682000_CIT0008","first-page":"439","article-title":"Identification of a novel germline SMARCB1 nonsense mutation in a family manifesting both schwannomatosis and unilateral vestibular schwannoma","volume-title":"J Neurooncol.","author":"Wu","year":"2015"},{"key":"2024080105583682000_CIT0009","first-page":"727","article-title":"Somatic mosaicism: a common cause of classic disease in tumor-prone syndromes? Lessons from type 2 neurofibromatosis","volume-title":"Am J Hum Genet.","author":"Evans","year":"1998"},{"key":"2024080105583682000_CIT0010","first-page":"16","article-title":"Neurofibromatosis type 2 (NF2): a clinical and molecular review","volume-title":"Orphanet J Rare Dis.","author":"Evans","year":"2009"},{"key":"2024080105583682000_CIT0011","first-page":"540","article-title":"Updated protocol for genetic testing, screening and clinical management of individuals at risk of NF2-related schwannomatosis","volume-title":"Clin Genet.","author":"Halliday","year":"2023"},{"key":"2024080105583682000_CIT0012","first-page":"97","article-title":"Bionano genome mapping: high-throughput, ultra-long molecule genome analysis system for precision genome assembly and haploid-resolved structural variation discovery","volume-title":"Adv Exp Med Biol.","author":"Bocklandt","year":"2019"},{"key":"2024080105583682000_CIT0013","doi-asserted-by":"crossref","DOI":"10.1101\/102764","article-title":"Rapid automated large structural variation detection in a diploid genome by NanoChannel based next-generation mapping","volume-title":"bioRxiv","author":"Hastie"},{"key":"2024080105583682000_CIT0014","first-page":"90","article-title":"Next-generation mapping: a novel approach for detection of pathogenic structural variants with a potential utility in clinical diagnosis","volume-title":"Genome Med.","author":"Barseghyan","year":"2017"},{"key":"2024080105583682000_CIT0015","first-page":"e1665","article-title":"Detection of a mosaic CDKL5 deletion and inversion by optical genome mapping ends an exhaustive diagnostic odyssey","volume-title":"Mol Genet Genomic Med.","author":"Cope","year":"2021"}],"container-title":["American Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajcp\/article-pdf\/162\/2\/110\/58687133\/aqae027.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajcp\/article-pdf\/162\/2\/110\/58687133\/aqae027.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T08:44:58Z","timestamp":1722501898000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajcp\/article\/162\/2\/110\/7634657"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,25]]},"references-count":15,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,3,25]]},"published-print":{"date-parts":[[2024,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ajcp\/aqae027","relation":{},"ISSN":["0002-9173","1943-7722"],"issn-type":[{"type":"print","value":"0002-9173"},{"type":"electronic","value":"1943-7722"}],"subject":[],"published-other":{"date-parts":[[2024,8]]},"published":{"date-parts":[[2024,3,25]]}}}