{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:19:29Z","timestamp":1792059569179,"version":"4.4.0"},"reference-count":29,"publisher":"BMJ","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1992,12]]},"abstract":"<jats:p>A clinical and genetic study of type 2 neurofibromatosis (NF2) has been carried out in the United Kingdom. Virtually complete ascertainment of cases in the north-west of England was achieved and suggests a population incidence of 1 in 33,000 to 40,000. In the UK as a whole, 150 cases have been identified and been used to study the clinical and genetic features of NF2. The autosomal dominant inheritance of NF2 was confirmed, 49% of cases were assessed as representing new mutations, and the mutation rate was estimated to be 6.5 x 10(-6). Evidence to support a maternal gene effect was found in that age at onset was 18.17 years in 36 maternally inherited cases and 24.5 in 20 paternally inherited cases (p = 0.027). The preponderance of maternally inherited cases was also significant (p = 0.03). Data are presented which suggest that there are two types of NF2, one with later onset and bilateral vestibular schwannomas as the only usual feature, and the other with earlier onset and multiple other tumours. A considerable number of cases did not fall easily into one or other group and other factors such as maternal effect on severity and anticipation need to be considered.<\/jats:p>","DOI":"10.1136\/jmg.29.12.841","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:23:16Z","timestamp":1226330596000},"page":"841-846","source":"Crossref","is-referenced-by-count":389,"title":["A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity."],"prefix":"10.1136","volume":"29","author":[{"given":"D G","family":"Evans","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S M","family":"Huson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Donnai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Neary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Blair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Teare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Newton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Strachan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Ramsden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1992,12,1]]},"reference":[{"issue":"18","key":"ref_1","first-page":"393","article-title":"Case of tumours in the skull, dura mater, and brain","volume":"1820","author":"Wishart, J.H.","unstructured":"Wishart JH. Case of tumours in the skull, dura mater, and brain. Edinburgh Med Surg,J 1820;18:393-7.","journal-title":"Edinburgh Med Surg, J"},{"key":"ref_2","article-title":"Ueber die multiplenfibroma der haut und ihre beziehung zu den multiplen neuromen","author":"F, Von Recklinghausen","year":"1882","unstructured":"Von Recklinghausen F. Ueber die multiplenfibroma der haut und ihre beziehung zu den multiplen neuromen. Berlin: A Hirschwald, 1882."},{"issue":"23","key":"ref_3","first-page":"266","article-title":"Bilateral acoustic neurofibromas: a clinical study and field survey of a family of five generations with bilateral deafness in thirty eight members","volume":"1930","author":"Gardner, W.J.; Frazier, C.H.","unstructured":"Gardner WJ, Frazier CH. Bilateral acoustic neurofibromas: a clinical study and field survey of a family of five generations with bilateral deafness in thirty eight members. Arch Neurol Psychiatr 1930;23:266-302.","journal-title":"Arch Neurol Psychiatr"},{"key":"ref_4","article-title":"A clinical, pathological and genetic study of multiple neurofibromatosis","author":"Crowe, F.W.; Schull, W.J.; Neal, J.V.","year":"1956","unstructured":"Crowe FW, Schull WJ, Neal JV. A clinical, pathological and genetic study of multiple neurofibromatosis. Springfield, Illinois: Charles C Thomas, 1956."},{"key":"ref_5","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_6","first-page":"213","article-title":"Central neurofibromatosis","volume":"55","author":"Huson, S.M.; Thrush, D.C.","year":"1985","unstructured":"Huson SM, Thrush DC. Central neurofibromatosis. Q 7 Med 1985;55:213-24."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1093\/brain\/111.6.1355","article-title":"Von Recklinghausen neurofibromatosis: a clinical and population based study in southeast Wales","volume":"111","author":"Huson, S.M.; Harper, P.S.; Compston, D.A.S.","year":"1988","unstructured":"Huson SM, Harper PS, Compston DAS. Von Recklinghausen neurofibromatosis: a clinical and population based study in southeast Wales. 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Cell 1987;49:589-94.","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1126\/science.3107130","article-title":"Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17","volume":"236","author":"Barker, D.; Wright, E.; Nguyen, K.","year":"1987","unstructured":"Barker D, Wright E, Nguyen K, et al. Gene for von Recklinghausen neurofibromatosis is in the pericentromeric region of chromosome 17. Science 1987;236:1100-2.","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/322644a0","article-title":"Loss of genes on chromosome 22 in tumorigenesis of human acoustic neuroma","volume":"322","author":"Seizinger, B.R.; Martuza, R.L.; Gusella, J.F.","year":"1986","unstructured":"Seizinger BR, Martuza RL, Gusella JF. Loss of genes on chromosome 22 in tumorigenesis of human acoustic neuroma. Nature 1986;322:644-7.","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/329246a0","article-title":"Genetic linkage analysis of bilateral acoustic neurofibromatosis to a DNA marker on chromosome 22","volume":"329","author":"Rouleau, G.; Seizinger, B.R.; Ozelius, L.G.","year":"1987","unstructured":"Rouleau G, Seizinger BR, Ozelius LG, et al. Genetic linkage analysis of bilateral acoustic neurofibromatosis to a DNA marker on chromosome 22. Nature 1987;329:246-8.","journal-title":"Nature"},{"key":"ref_13","first-page":"88","article-title":"Multiple meningeal and perineural tumours with analagous changes in the glia and ependyma (neurofibroblastomatosis)","volume":"60","author":"Worster-Drought, C.; Dickson, W.E.C.; McMenemey, W.H.","year":"1937","unstructured":"Worster-Drought C, Dickson WEC, McMenemey WH. Multiple meningeal and perineural tumours with analagous changes in the glia and ependyma (neurofibroblastomatosis). Brain 1937;60:88-117.","journal-title":"Brain"},{"key":"ref_14","first-page":"32","article-title":"Neurofibromatosis 2: clinical heterogeneity and natural history in 39 individuals","volume":"49","author":"Eldridge, R.; Parry, D.M.; Kaiser-Kupfer, M.I.","year":"1991","unstructured":"Eldridge R, Parry DM, Kaiser-Kupfer MI. Neurofibromatosis 2: clinical heterogeneity and natural history in 39 individuals in 9 families and 16 sporadic cases. AmJ Hum Genet 1991;49:32.","journal-title":"9 families and; AmJ Hum Genet; sporadic cases"},{"key":"ref_15","first-page":"154","article-title":"Familial central nervous system neoplasia","volume":"20","author":"Lee, D.K.; Abbott, M.L.","year":"1969","unstructured":"Lee DK, Abbott ML. Familial central nervous system neoplasia. 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Estimation of relative fitness in human abnormalities with sex difference in selection intensity: a new simplified method. Jinrui Idengaku Zasshi 1975;20:183-6.","journal-title":"Jinrui Idengaku Zasshi"},{"key":"ref_19","article-title":"Methodology in medical genetics","author":"Emery, A.E.H.","year":"1986","unstructured":"Emery AEH. Methodology in medical genetics. Edinburgh: Churchill Livingstone, 1986."},{"key":"ref_20","first-page":"117","article-title":"A simple exact test for birth order effect","volume":"14","author":"Haldane, J.B.S.; Smith, C.A.B.","year":"1947","unstructured":"Haldane JBS, Smith CAB. A simple exact test for birth order effect. Ann Eugen 1947;14:117-24."},{"key":"ref_21","first-page":"847","article-title":"A genetic study of type 2 neurofibromatosis. II. Guidelines for genetic counselling. J7 Med","volume":"29","author":"Evans, D.G.R.; Huson, S.; Donnai, D.","year":"1992","unstructured":"Evans DGR, Huson S, Donnai D, et al. A genetic study of type 2 neurofibromatosis. II. Guidelines for genetic counselling. J7 Med Genet 1992;29:847-52.","journal-title":"Genet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/355545a0","article-title":"Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy","volume":"355","author":"Harley, H.G.; Brook, D.J.; Rundle, S.A.","year":"1992","unstructured":"Harley HG, Brook DJ, Rundle SA, et al. Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy. Nature 1992;355:545-51.","journal-title":"Nature"},{"key":"ref_23","article-title":"Type 2 neurofibromatosis: the need for supraregional care?","author":"Evans, D.G.R.; Ramsden, R.; Harris, R.; Lye, R.; Huson, S.M.; King, T.T.","unstructured":"Evans DGR, Ramsden R, Harris R, Lye R, Huson SM, King TT. Type 2 neurofibromatosis: the need for supraregional care? J Laryngol Otol (in press).","journal-title":"J Laryngol Otol"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1227\/00006123-198201000-00001","article-title":"Bilateral acoustic neuromas: clinical aspects, pathogenesis and treatment","volume":"10","author":"Martuza, R.L.; Ojemann, R.G.","year":"1982","unstructured":"Martuza RL, Ojemann RG. Bilateral acoustic neuromas: clinical aspects, pathogenesis and treatment. Neurosurgery 1982;10: 1-12.","journal-title":"Neurosurgery"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1288\/00005537-198707000-00001","article-title":"Acoustic neuroma surgery: the results of hearing conservation surgery","volume":"97","author":"Glasscock, M.E.; McKennan, K.X.; Levine, S.C.","year":"1987","unstructured":"Glasscock ME, McKennan KX, Levine SC. Acoustic neuroma surgery: the results of hearing conservation surgery. Laryngoscope 1987;97:785-9.","journal-title":"Laryngoscope"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1001\/archotol.1968.00770010702019","article-title":"Bilateral acoustic tumours and neurofibromatosis","volume":"88","author":"Hitselberger, W.E.; Hughes, R.L.","year":"1968","unstructured":"Hitselberger WE, Hughes RL. Bilateral acoustic tumours and neurofibromatosis. Arch Otolaryngol 1968;88:700-1 1.","journal-title":"Arch Otolaryngol"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1136\/jmg.26.11.704","article-title":"A genetic study of von Recklinghausen neurofibromatosis in south east Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity","volume":"26","author":"Huson, S.M.; Compston, D.A.S.; Clark, P.; Harper, P.S.","year":"1989","unstructured":"Huson SM, Compston DAS, Clark P, Harper PS. A genetic study of von Recklinghausen neurofibromatosis in south east Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity. Jf Med Genet 1989;26:704-1 1.","journal-title":"Jf Med Genet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1136\/jmg.28.7.443","article-title":"Von Hippel-Lindau disease: a genetic study","volume":"28","author":"Maher, E.R.; Iselius, L.; Yates, J.R.W.","year":"1991","unstructured":"Maher ER, Iselius L, Yates JRW, et al. Von Hippel-Lindau disease: a genetic study. J Med Genet 1991;28:443-7. Hall JG.","journal-title":"J Med Genet"},{"key":"ref_29","first-page":"357","article-title":"There is no neurofibromatosis non-allelic genetic heterogeneity in type 2","volume":"49","author":"Rouleau, G.A.; Narod, S.A.; Faucher, J.A.; Haines, J.A.; Gusella, J.F.","year":"1991","unstructured":"Rouleau GA, Narod SA, Faucher JA, Haines JA, Gusella JF. There is no neurofibromatosis non-allelic genetic heterogeneity in type 2. 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