{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T02:20:20Z","timestamp":1785464420458,"version":"3.56.0"},"reference-count":26,"publisher":"BMJ","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1998,6]]},"abstract":"<jats:p>Blood samples from 125 unrelated families with classical type 2 neurofibromatosis (NF2) with bilateral vestibular schwannomas have been analysed for mutations in the NF2 gene. A further 17 families fulfilling modified criteria for NF2 have also been analysed. Causative mutations have been identified in 54 (43%) classical families and six (35%) of those fulfilling modified criteria. Forty-two cases from 38 families with truncating mutations had an average age at onset of symptoms of 19 years and diagnosis at 22.4 years. Fifty-one cases from 16 families with splice site mutations (15 from six), missense mutations (18 from six), and large deletions (18 from five) had an average age of onset of 27.8 years and at diagnosis of 33.4 years. Subjects with truncating mutations were significantly more likely to have symptoms before 20 years of age (p&lt;0.001) and to develop at least two symptomatic CNS tumours in addition to vestibular schwannoma before 30 years (p&lt;0.001). There were also significantly fewer multigenerational families with truncating mutations. Four further truncating mutations were in mosaic form and were associated with milder disease than other similar mutations. This large study has confirmed the previous impression that truncating mutations are associated with severe disease, but caution has to be exercised in using mutation type to predict disease course.<\/jats:p>","DOI":"10.1136\/jmg.35.6.450","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"450-455","source":"Crossref","is-referenced-by-count":186,"title":["Genotype\/phenotype correlations in type 2 neurofibromatosis (NF2): evidence for more severe disease associated with truncating mutations."],"prefix":"10.1136","volume":"35","author":[{"given":"D G","family":"Evans","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Trueman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Wallace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Strachan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1998,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1212\/WNL.30.8.851","article-title":"Central neurofibromatosis with bilateral acoustic neuroma. Genetic, clinical and biochemical distinctions from peripheral neurofibromatosis","volume":"30","author":"Kanter, W.R.; Eldridge, R.; Fabricant, R.; Allen, J.C.; Koerber, T.","year":"1980","unstructured":"Kanter WR, Eldridge R, Fabricant R, Allen JC, Koerber T. Central neurofibromatosis with bilateral acoustic neuroma. Genetic, clinical and biochemical distinctions from peripheral neurofibromatosis. Neurology 1980;30:851-9.","journal-title":"Neurology"},{"key":"ref_2","first-page":"603","article-title":"A clinical study of type 2 neurofibromatosis. QJfMed","volume":"84","author":"Evans, D.G.R.; Huson, S.M.; Donnai, D.","year":"1992","unstructured":"Evans DGR, Huson SM, Donnai D, et al. A clinical study of type 2 neurofibromatosis. QJfMed 1992;84:603-18."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1002\/ajmg.1320520411","article-title":"Neurofibromatosis 2 (NF2): clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity","volume":"52","author":"Parry, D.M.; Eldridge, R.; Kaiser-Kupfer, M.I.; Bouzas, E.A.; Pikus, A.; Patronas, N.","year":"1994","unstructured":"Parry DM, Eldridge R, Kaiser-Kupfer MI, Bouzas EA, Pikus A, Patronas N. Neurofibromatosis 2 (NF2): clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity. Am J Med Genet 1994;52:450-1.","journal-title":"Am J Med Genet"},{"key":"ref_4","first-page":"3","article-title":"Health Consensus Development Conference Statement on Neurofibromatosis","volume":"3","author":"National Institutes of","year":"1987","unstructured":"National Institutes of Health Consensus Development Conference Statement on Neurofibromatosis. Neurofibromatosis Res Newsl 1987;3:3-6.","journal-title":"Neurofibromatosis Res Newsl"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/363515a0","article-title":"Alteration in a new gene encoding a putative membrane-organizing protein causes neurofibromatosis type 2","volume":"363","author":"Rouleau, G.A.; Merel, P.; Lutchman, M.","year":"1993","unstructured":"Rouleau GA, Merel P, Lutchman M, et al. Alteration in a new gene encoding a putative membrane-organizing protein causes neurofibromatosis type 2. Nature 1993;363: 515-21.","journal-title":"Nature"},{"key":"ref_6","first-page":"791800","article-title":"A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor","volume":"72","author":"Troffater, J.A.; MacCollin, M.M.; Rutter, J.L.","year":"1993","unstructured":"Troffater JA, MacCollin MM, Rutter JL, et al. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Cell 1993;72:791800.","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/gcc.2870120206","article-title":"Screening for germ-line mutations in the NF2 gene","volume":"12","author":"Merel, P.; Hoang-Xuan, K.; Sansom, M.","year":"1995","unstructured":"Merel P, Hoang-Xuan K, Sansom M, et al. Screening for germ-line mutations in the NF2 gene. Genes Chrom Cancer 1995;12:117-27.","journal-title":"Genes Chrom Cancer"},{"key":"ref_8","first-page":"529","article-title":"Germ-line mutations in the neurofibromatosis 2 gene: correlations with disease severity and retinal abnormalities","volume":"59","author":"Parry, D.M.; MacCollin, M.; Kaiser-Kupfer, M.I.","year":"1996","unstructured":"Parry DM, MacCollin M, Kaiser-Kupfer MI, et al. 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Cancer Res 1993;53:2728-31.","journal-title":"Cancer Res"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1212\/WNL.46.4.1072","article-title":"Schwannomatosis: a clinical and pathological study","volume":"46","author":"MacCollin, M.; Woodfin, W.; Kronn, D.; Short, M.P.","year":"1996","unstructured":"MacCollin M, Woodfin W, Kronn D, Short MP. Schwannomatosis: a clinical and pathological study. Neurology 1996;46:1072-9.","journal-title":"Neurology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1093\/hmg\/4.1.137","article-title":"High frequency of nonsense mutations in the NF2 gene caused by C to T transitions in five CGA codons","volume":"4","author":"Sainz, S.; Figuero, K.; Baser, M.E.; Mautner, V.F.; Pulst, S.","year":"1995","unstructured":"Sainz S, Figuero K, Baser ME, Mautner VF, Pulst S. High frequency of nonsense mutations in the NF2 gene caused by C to T transitions in five CGA codons. Hum Mol Genet 1995;4: 137-9.","journal-title":"Hum Mol Genet"},{"key":"ref_25","first-page":"54","article-title":"Phenotypic variability in monozygotic twins with neurofibromatosis 2","volume":"57","author":"Baser, M.E.; Ragge, N.K.; Riccardi, V.; Janus, T.; Gantz, B.; Pulst, S.","year":"1995","unstructured":"Baser ME, Ragge NK, Riccardi V,Janus T, Gantz B, Pulst S. Phenotypic variability in monozygotic twins with neurofibromatosis 2. AmJ Med Genet 1995;57:A54.","journal-title":"AmJ Med Genet"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1017\/S002221510012328X","article-title":"Type 2 neurofibromatosis: the need for supraregional care","volume":"107","author":"Evans, D.G.R.; Ramsden, R.; Huson, S.M.","year":"1993","unstructured":"Evans DGR, Ramsden R, Huson SM, et al. Type 2 neurofibromatosis: the need for supraregional care. J LaryngolOtol 1993;107:401-6.","journal-title":"J LaryngolOtol"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.35.6.450","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T04:43:22Z","timestamp":1760762602000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.35.6.450"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,6]]},"references-count":26,"journal-issue":{"issue":"6","published-online":{"date-parts":[[1998,6,1]]},"published-print":{"date-parts":[[1998,6]]}},"alternative-id":["10.1136\/jmg.35.6.450"],"URL":"https:\/\/doi.org\/10.1136\/jmg.35.6.450","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,6]]}}}