Neurofibromatosis type 2 attributable to gonosomal mosaicism in a clinically normal mother, and identification of seven novel mutations in the NF2 gene

Neurofibromatosis type 2 (NF2) is an autosomal dominant cancer syndrome tha t preisposes to the development of bilateral vestibular schwannomas sometim es associated with schwannomas at other locations, meningiomas. ependymomas and juvenile posterior subcapsular lenticular opacities. This disease is c aused by inactivating mutations in the NF2 tumour-suppressor gene, located in 22q12. Recently, somatic mosaicism has been demonstrated in some "de nov o" NF2 patients. We here report the genetic study of 33 NF2 patients from 3 3 unrelated Italian families. Twelve mutations were characterised, includin g seven newly identified mutations and five recurrent ones. Furthermore, we describe one patient with an inactivating mutation that lies in exon 13 bu t that is present in only a portion of the lymphocytes and, more importantl y, a clinically normal individual carrying a somatic/germinal mosaicism for a nonsense mutation in exon 10 of the NF2 gene. Our results confirm the re latively high percentage of mosaicism for mutations in the NF2 ene and esta blish the importance of evaluating genomic DNA from several tissues, in add ition to lymphocytes, so as to identify mosaicism in "de novo" NF2 patients and their relatives. In addition, the demonstration of somatic and/or gona dal mosaicism is an important tool for accurate genetic counselling in fami lies with sporadic cases of NF2.