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Clinical and molecular predictors of mortality in neurofibromatosis 2: a UK national analysis of 1192 patients

BackgroundNeurofibromatosis 2 (NF2) is an autosomal-dominant tumour predisposition syndrome characterised by bilateral vestibular schwannomas, considerable morbidity and reduced life expectancy. Although genotype–phenotype correlations are well established in NF2, little is known about effects of mu... Full description

Journal Title: Journal of Medical Genetics 2015-10, Vol.52 (10), p.699-705
Main Author: Hexter, Adam
Other Authors: Jones, Adrian , Joe, Harry , Heap, Laura , Smith, Miriam J , Wallace, Andrew J , Halliday, Dorothy , Parry, Allyson , Taylor, Amy , Raymond, Lucy , Shaw, Adam , Afridi, Shazia , Obholzer, Rupert , Axon, Patrick , King, Andrew T , Friedman, Jan M , Evans, D Gareth R
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: England: British Medical Association
ID: ISSN: 0022-2593
Link: https://www.ncbi.nlm.nih.gov/pubmed/26275417
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title: Clinical and molecular predictors of mortality in neurofibromatosis 2: a UK national analysis of 1192 patients
format: Article
creator:
  • Hexter, Adam
  • Jones, Adrian
  • Joe, Harry
  • Heap, Laura
  • Smith, Miriam J
  • Wallace, Andrew J
  • Halliday, Dorothy
  • Parry, Allyson
  • Taylor, Amy
  • Raymond, Lucy
  • Shaw, Adam
  • Afridi, Shazia
  • Obholzer, Rupert
  • Axon, Patrick
  • King, Andrew T
  • Friedman, Jan M
  • Evans, D Gareth R
subjects:
  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Female
  • Gene mutations
  • Genes, Neurofibromatosis 2
  • Genetic aspects
  • Genetic Association Studies
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • Mutation
  • Neurofibromatosis
  • Neurofibromatosis 2 - diagnosis
  • Neurofibromatosis 2 - genetics
  • Neurofibromatosis 2 - mortality
  • Patient outcomes
  • Risk factors
  • United Kingdom
ispartof: Journal of Medical Genetics, 2015-10, Vol.52 (10), p.699-705
description: BackgroundNeurofibromatosis 2 (NF2) is an autosomal-dominant tumour predisposition syndrome characterised by bilateral vestibular schwannomas, considerable morbidity and reduced life expectancy. Although genotype–phenotype correlations are well established in NF2, little is known about effects of mutation type or location within the gene on mortality. Improvements in NF2 diagnosis and management have occurred, but their effect on patient survival is unknown.MethodsWe evaluated clinical and molecular predictors of mortality in 1192 patients (771 with known causal mutations) identified through the UK National NF2 Registry. Kaplan–Meier survival and Cox regression analyses were used to evaluate predictors of mortality, with jackknife adjustment of parameter SEs to account for the strong intrafamilial phenotypic correlations that occur in NF2.ResultsThe study included 241 deaths during 10 995 patient-years of follow-up since diagnosis. Early age at diagnosis and the presence of intracranial meningiomas were associated with increased mortality, and having a mosaic, rather than non-mosaic, NF2 mutation was associated with reduced mortality. Patients with splice-site or missense mutations had lower mortality than patients with truncating mutations (OR 0.459, 95% CI 0.213 to 0.990, and OR 0.196, 95% CI 0.213 to 0.990, respectively). Patients with splice-site mutations in exons 6–15 had lower mortality than patients with splice-site mutations in exons 1–5 (OR 0.333, 95% CI 0.129 to 0.858). The mortality of patients with NF2 diagnosed in more recent decades was lower than that of patients diagnosed earlier.ConclusionsContinuing advances in molecular diagnosis, imaging and treatment of NF2-associated tumours offer hope for even better survival in the future.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0022-2593
fulltext: fulltext
issn:
  • 0022-2593
  • 1468-6244
url: Link


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titleClinical and molecular predictors of mortality in neurofibromatosis 2: a UK national analysis of 1192 patients
sourceAlma/SFX Local Collection
creatorHexter, Adam ; Jones, Adrian ; Joe, Harry ; Heap, Laura ; Smith, Miriam J ; Wallace, Andrew J ; Halliday, Dorothy ; Parry, Allyson ; Taylor, Amy ; Raymond, Lucy ; Shaw, Adam ; Afridi, Shazia ; Obholzer, Rupert ; Axon, Patrick ; King, Andrew T ; Friedman, Jan M ; Evans, D Gareth R
creatorcontribHexter, Adam ; Jones, Adrian ; Joe, Harry ; Heap, Laura ; Smith, Miriam J ; Wallace, Andrew J ; Halliday, Dorothy ; Parry, Allyson ; Taylor, Amy ; Raymond, Lucy ; Shaw, Adam ; Afridi, Shazia ; Obholzer, Rupert ; Axon, Patrick ; King, Andrew T ; Friedman, Jan M ; Evans, D Gareth R ; English Specialist NF2 Research Group ; The English Specialist NF2 Research Group
descriptionBackgroundNeurofibromatosis 2 (NF2) is an autosomal-dominant tumour predisposition syndrome characterised by bilateral vestibular schwannomas, considerable morbidity and reduced life expectancy. Although genotype–phenotype correlations are well established in NF2, little is known about effects of mutation type or location within the gene on mortality. Improvements in NF2 diagnosis and management have occurred, but their effect on patient survival is unknown.MethodsWe evaluated clinical and molecular predictors of mortality in 1192 patients (771 with known causal mutations) identified through the UK National NF2 Registry. Kaplan–Meier survival and Cox regression analyses were used to evaluate predictors of mortality, with jackknife adjustment of parameter SEs to account for the strong intrafamilial phenotypic correlations that occur in NF2.ResultsThe study included 241 deaths during 10 995 patient-years of follow-up since diagnosis. Early age at diagnosis and the presence of intracranial meningiomas were associated with increased mortality, and having a mosaic, rather than non-mosaic, NF2 mutation was associated with reduced mortality. Patients with splice-site or missense mutations had lower mortality than patients with truncating mutations (OR 0.459, 95% CI 0.213 to 0.990, and OR 0.196, 95% CI 0.213 to 0.990, respectively). Patients with splice-site mutations in exons 6–15 had lower mortality than patients with splice-site mutations in exons 1–5 (OR 0.333, 95% CI 0.129 to 0.858). The mortality of patients with NF2 diagnosed in more recent decades was lower than that of patients diagnosed earlier.ConclusionsContinuing advances in molecular diagnosis, imaging and treatment of NF2-associated tumours offer hope for even better survival in the future.
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subjectAdolescent ; Adult ; Child ; Child, Preschool ; Female ; Gene mutations ; Genes, Neurofibromatosis 2 ; Genetic aspects ; Genetic Association Studies ; Humans ; Infant ; Kaplan-Meier Estimate ; Male ; Mutation ; Neurofibromatosis ; Neurofibromatosis 2 - diagnosis ; Neurofibromatosis 2 - genetics ; Neurofibromatosis 2 - mortality ; Patient outcomes ; Risk factors ; United Kingdom
ispartofJournal of Medical Genetics, 2015-10, Vol.52 (10), p.699-705
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2Copyright: 2015 Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions
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2Joe, Harry
3Heap, Laura
4Smith, Miriam J
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9Raymond, Lucy
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descriptionBackgroundNeurofibromatosis 2 (NF2) is an autosomal-dominant tumour predisposition syndrome characterised by bilateral vestibular schwannomas, considerable morbidity and reduced life expectancy. Although genotype–phenotype correlations are well established in NF2, little is known about effects of mutation type or location within the gene on mortality. Improvements in NF2 diagnosis and management have occurred, but their effect on patient survival is unknown.MethodsWe evaluated clinical and molecular predictors of mortality in 1192 patients (771 with known causal mutations) identified through the UK National NF2 Registry. Kaplan–Meier survival and Cox regression analyses were used to evaluate predictors of mortality, with jackknife adjustment of parameter SEs to account for the strong intrafamilial phenotypic correlations that occur in NF2.ResultsThe study included 241 deaths during 10 995 patient-years of follow-up since diagnosis. Early age at diagnosis and the presence of intracranial meningiomas were associated with increased mortality, and having a mosaic, rather than non-mosaic, NF2 mutation was associated with reduced mortality. Patients with splice-site or missense mutations had lower mortality than patients with truncating mutations (OR 0.459, 95% CI 0.213 to 0.990, and OR 0.196, 95% CI 0.213 to 0.990, respectively). Patients with splice-site mutations in exons 6–15 had lower mortality than patients with splice-site mutations in exons 1–5 (OR 0.333, 95% CI 0.129 to 0.858). The mortality of patients with NF2 diagnosed in more recent decades was lower than that of patients diagnosed earlier.ConclusionsContinuing advances in molecular diagnosis, imaging and treatment of NF2-associated tumours offer hope for even better survival in the future.
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titleClinical and molecular predictors of mortality in neurofibromatosis 2: a UK national analysis of 1192 patients
authorHexter, Adam ; Jones, Adrian ; Joe, Harry ; Heap, Laura ; Smith, Miriam J ; Wallace, Andrew J ; Halliday, Dorothy ; Parry, Allyson ; Taylor, Amy ; Raymond, Lucy ; Shaw, Adam ; Afridi, Shazia ; Obholzer, Rupert ; Axon, Patrick ; King, Andrew T ; Friedman, Jan M ; Evans, D Gareth R
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atitleClinical and molecular predictors of mortality in neurofibromatosis 2: a UK national analysis of 1192 patients
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volume52
issue10
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abstractBackgroundNeurofibromatosis 2 (NF2) is an autosomal-dominant tumour predisposition syndrome characterised by bilateral vestibular schwannomas, considerable morbidity and reduced life expectancy. Although genotype–phenotype correlations are well established in NF2, little is known about effects of mutation type or location within the gene on mortality. Improvements in NF2 diagnosis and management have occurred, but their effect on patient survival is unknown.MethodsWe evaluated clinical and molecular predictors of mortality in 1192 patients (771 with known causal mutations) identified through the UK National NF2 Registry. Kaplan–Meier survival and Cox regression analyses were used to evaluate predictors of mortality, with jackknife adjustment of parameter SEs to account for the strong intrafamilial phenotypic correlations that occur in NF2.ResultsThe study included 241 deaths during 10 995 patient-years of follow-up since diagnosis. Early age at diagnosis and the presence of intracranial meningiomas were associated with increased mortality, and having a mosaic, rather than non-mosaic, NF2 mutation was associated with reduced mortality. Patients with splice-site or missense mutations had lower mortality than patients with truncating mutations (OR 0.459, 95% CI 0.213 to 0.990, and OR 0.196, 95% CI 0.213 to 0.990, respectively). Patients with splice-site mutations in exons 6–15 had lower mortality than patients with splice-site mutations in exons 1–5 (OR 0.333, 95% CI 0.129 to 0.858). The mortality of patients with NF2 diagnosed in more recent decades was lower than that of patients diagnosed earlier.ConclusionsContinuing advances in molecular diagnosis, imaging and treatment of NF2-associated tumours offer hope for even better survival in the future.
copEngland
pubBritish Medical Association
pmid26275417
doi10.1136/jmedgenet-2015-103290