Mosaicism in neurofibromatosis type 2: an update of risk based on uni/bilaterality of vestibular schwannoma at presentation and sensitive mutation analysis including multiple ligation-dependent probe amplification

Background: Neurofibromatosis type 2 (NF2) is almost unique among inherited disorders in the frequency of mosaicism in the first affected generation. However, the implications of this on transmission risks have not been fully elucidated. Methods: The expanded database of 460 families with NF2 and 70...

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Vydané v:	Journal of medical genetics Ročník 44; číslo 7; s. 424 - 428
Hlavní autori:	Evans, D Gareth R, Ramsden, R T, Shenton, A, Gokhale, C, Bowers, N L, Huson, S M, Pichert, G, Wallace, A
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London BMJ Publishing Group Ltd 01.07.2007 BMJ BMJ Publishing Group LTD BMJ Group
Predmet:	Biological and medical sciences Deoxyribonucleic acid DNA DNA Mutational Analysis FISH fluorescence in situ hybridisation Fundamental and applied biological sciences. Psychology General aspects. Genetic counseling Genetic Predisposition to Disease Genetics of eukaryotes. Biological and molecular evolution Humans In Situ Hybridization, Fluorescence Lymphocytes Medical genetics Medical sciences MLPA Molecular and cellular biology Molecular Probe Techniques Mosaicism multiple ligation-dependent probe amplification Mutation Neurofibromatosis 2 - complications Neurofibromatosis 2 - genetics neurofibromatosis type 2 Neurology Neuroma, Acoustic - etiology NF2 Nucleic Acid Amplification Techniques Original Patients Pedigree Polymorphism, Single-Stranded Conformational Risk Assessment Tumors Tumors of the nervous system. Phacomatoses unilateral vestibular schwannoma UVS vestibular schwannoma Human Vestibular nerve Neurofibromatosis II Nervous system diseases Multiple Neurinoma Risk Gene amplification Ligature Risk factor Genetics Mosaicism Molecular probe Benign neoplasm Mutation
ISSN:	0022-2593, 1468-6244, 1468-6244
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Shrnutí:	Background: Neurofibromatosis type 2 (NF2) is almost unique among inherited disorders in the frequency of mosaicism in the first affected generation. However, the implications of this on transmission risks have not been fully elucidated. Methods: The expanded database of 460 families with NF2 and 704 affected individuals was analysed for mosaicism and transmission risks to offspring. Results: 64 mosaic patients, with a projected mosaicism rate of 33% for sporadic classical NF2 with bilateral vestibular schwannoma at presentation and 60% for those presenting unilaterally, were identified. Offspring risks can be radically reduced on the basis of a sensitive mutation analysis of blood DNA including multiple ligation-dependent probe amplification (MLPA, which detects 15% of all mutations), but even MLPA cannot detect high levels of mosaicism. Conclusion: The chances of mosaicism in NF2 and the resultant risks of transmission of the mutation to offspring in a number of different clinical situations have been further delineated. The use of MLPA in this large NF2 series is also reported for the first time.
Bibliografia:	Correspondence to:  Professor D G R Evans  Department of Medical Genetics, St Mary’s Hospital, Hathersage Road, Manchester M13 0JH, UK;gareth.evans@cmmc.nhs.uk PMID:17307835 local:0440424 ark:/67375/NVC-RWDX8ZCL-B istex:F929FDC01DAB26001DF8F88EEA9837A45DFDCF96 href:jmedgenet-44-424.pdf ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0022-2593 1468-6244 1468-6244
DOI:	10.1136/jmg.2006.047753