{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:10:14Z","timestamp":1791382214949,"version":"4.3.3"},"reference-count":20,"publisher":"BMJ","issue":"9","funder":[{"name":"NHS England"},{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203308"],"award-info":[{"award-number":["NIHR203308"]}],"id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2024,6,14]]},"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>New diagnostic criteria for NF2-related schwannomatosis (NF2) were published in 2022. An updated UK prevalence was generated in accordance with these, with an emphasis on the rate of de novo NF2 (a 50% frequency is widely quoted in genetic counselling). The distribution of variant types among de novo and familial NF2 cases was also assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The UK National NF2 database identifies patients meeting updated NF2 criteria from a highly ascertained population cared for by England\u2019s specialised service. Diagnostic prevalence was assessed on 1 February 2023. Molecular analysis of blood and, where possible, tumour specimens for\n                      <jats:italic>NF2, LZTR1<\/jats:italic>\n                      and\n                      <jats:italic>SMARCB1<\/jats:italic>\n                      was performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      1084 living NF2 patients were identified on prevalence day (equivalent to 1 in 61 332). The proportion with NF2 inherited from an affected parent was only 23% in England. If people without a confirmed molecular diagnosis or bilateral vestibular schwannoma are excluded, the frequency of de novo NF2 remains high (72%). Of the identified de novo cases, almost half were mosaic. The most common variant type was nonsense variants, accounting for 173\/697 (24.8%) of people with an established variant, but only 18\/235 (7.7%) with an inherited\n                      <jats:italic>NF2<\/jats:italic>\n                      pathogenic variant (p&lt;0.0001). Missense variants had the highest proportion of familial association (56%). The prevalence of\n                      <jats:italic>LZTR1<\/jats:italic>\n                      -related schwannomatosis and\n                      <jats:italic>SMARCB1<\/jats:italic>\n                      -related schwannomatosis was 1 in 527\u2009000 and 1 in 1.1M, respectively, 8.4\u201318.4 times lower than NF2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This work confirms a much higher rate of de novo NF2 than previously reported and highlights the benefits of maintaining patient databases for accurate counselling.<\/jats:p>\n                  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Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9360-8194","authenticated-orcid":false,"given":"George J","family":"Burghel","sequence":"additional","affiliation":[{"name":"Genomic Diagnostic Laboratory, Manchester University NHS Foundation Trust, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Bowers","sequence":"additional","affiliation":[{"name":"North West Genomic Laboratory Hub, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Roberts","sequence":"additional","affiliation":[{"name":"Genomic Medicine, MFT, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Lavin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Manchester Academic Health Sciences Centre (MAHSC), Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Halliday","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Salford Royal Hospital, Salford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew Thomas","family":"King","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Salford Royal Hospital, Salford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Rutherford","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Salford Royal Hospital, Salford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar N","family":"Pathmanaban","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Salford Royal Hospital, Salford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Lloyd","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Freeman","sequence":"additional","affiliation":[{"name":"Otolaryngology, Salford Royal NHS Foundation Trust, Salford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy","family":"Halliday","sequence":"additional","affiliation":[{"name":"Oxford Centre for Genetic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK"},{"name":"Neurosciences, NF2 Unit, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allyson","family":"Parry","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oxford Radcliffe Hospitals NHS Trust, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Axon","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6344-371X","authenticated-orcid":false,"given":"Juliette","family":"Buttimore","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shazia","family":"Afridi","sequence":"additional","affiliation":[{"name":"Guy's and St Thomas' Hospitals NHS Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupert","family":"Obholzer","sequence":"additional","affiliation":[{"name":"ENT and Skull Base Surgery, Guy's and St Thomas' NHS Foundation Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Laitt","sequence":"additional","affiliation":[{"name":"Northern Care Alliance NHS Foundation Trust, Salford, Manchester, 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