Mosaicism in sporadic neurofibromatosis 2 patients

More than half of neurofibromatosis 2 (NF2) patients represent de novo muta tions which could have occurred at either pre-zygotic or post-zygotic stage s. A post-zygotic mutation can result in mosaicism, In four sporadic NF2 pa tients, we found NF2 mutations in only a portion of corresponding leukocyte s, In two other sporadic patients, no mutations were found in leukocytes bu t constitutional NF2 mutations were suggested by identical mutations in dif ferent tumors from each patient. We screened leukocyte DNA from 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) 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 cas es, 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 smal l populations of mutation-bearing cells can in some cases result in mild ph enotypes and can also lead to difficulties in identifying mutations. No mut ations 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 le ukocytes. These findings suggest that mosaicism is relatively common in NF2 and may have important implications for diagnosis, prognosis and genetic c ounseling.