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 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.


CONCLUSIONS
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.
Evans
D Gareth R
DG
Academic Unit of Medical Genetics and Regional Genetics Service, St Mary's Hospital, Manchester, UK. gareth.evans@cmmc.nhs.uk
Ramsden
R T
RT
Shenton
A
A
Gokhale
C
C
Bowers
N L
NL
Huson
S M
SM
Pichert
G
G
Wallace
A
A
D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015336:Molecular Probe Techniques; D009030:Mosaicism; D016518:Neurofibromatosis 2 / Q000150:complications* / Q000235:genetics*; D009464:Neuroma, Acoustic / Q000209:etiology*; D021141:Nucleic Acid Amplification Techniques; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D018570:Risk Assessment