Human Molecular Genetics, Vol 7, 2051-2055, Copyright © 1998 by Oxford University Press
L Kluwe and VF Mautner
More than half of neurofibromatosis 2 (NF2) patients represent de novo
mutations which could have occurred at either pre-zygotic or post- zygotic
stages. A post-zygotic mutation can result in mosaicism. In four sporadic
NF2 patients, we found NF2 mutations in only a portion of corresponding
leukocytes. In two other sporadic patients, no mutations were found in
leukocytes but constitutional NF2 mutations were suggested by identical
mutations in different tumors from each patient. We screened leukocyte DNA
from a total of 16 inherited and 91 sporadic NF2 patients, and found NF2
mutations in 13 (81%) of the former and in 46 (51%) of the latter cases.
The 30% difference in the rate of detection of mutations ( P = 0.051) might
be partially explained by mosaicism in a portion of sporadic NF2 patients
who carry the mutations in such a fashion that their leukocytes are
unaffected. Among sporadic cases, we found mutations more frequently in
patients with severe phenotypes (59%) than in patients with mild phenotypes
(23%) (difference of 36%, P = 0.007). Mosaicism might be more common in the
latter patient group since small populations of mutation-bearing cells can
in some cases result in mild phenotypes and can also lead to difficulties
in identifying mutations. No mutations were found in eight patients
suspected of having NF2. Mosaicism with an extremely small population of
affected cells may explain the incomplete phenotypes in some of these
patients and the lack of mutations in their leukocytes. These findings
suggest that mosaicism is relatively common in NF2 and may have important
implications for diagnosis, prognosis and genetic counseling.
ARTICLES
Mosaicism in sporadic neurofibromatosis 2 patients
Laboratory for Brain Tumor Biology, Department of Neurosurgery, University Hospital Eppendorf, Germany. kluwe@uke.uni-hamburg.de
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