Mosaicism in sporadic neurofibromatosis 2 patients

More than half of neurofibromatosis 2 (NF2) patients represent de novomutations which could have occurred at either pre-zygotic or post- zygoticstages. A post-zygotic mutation can result in mosaicism. In four sporadicNF2 patients, we found NF2 mutations in only a portion of correspondingleukocytes. In two other sporadic patients, no mutations were found inleukocytes but constitutional NF2 mutations were suggested by identicalmutations in different tumors from each patient. We screened leukocyte DNAfrom a total of 16 inherited and 91 sporadic NF2 patients, and found NF2mutations 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) mightbe partially explained by mosaicism in a portion of sporadic NF2 patientswho carry the mutations in such a fashion that their leukocytes areunaffected. Among sporadic cases, we found mutations more frequently inpatients with severe phenotypes (59%) than in patients with mild phenotypes(23%) (difference of 36%, P = 0.007). Mosaicism might be more common in thelatter patient group since small populations of mutation-bearing cells canin some cases result in mild phenotypes and can also lead to difficultiesin identifying mutations. No mutations were found in eight patientssuspected of having NF2. Mosaicism with an extremely small population ofaffected cells may explain the incomplete phenotypes in some of thesepatients and the lack of mutations in their leukocytes. These findingssuggest that mosaicism is relatively common in NF2 and may have importantimplications for diagnosis, prognosis and genetic counseling.