Familial brain tumour syndrome associated with a p53 germline deletion of codon 236

This report describes clinical, neuropathological and molecular genetic findings in a Swiss family with four brain tumours in only two generations. The neoplasms observed covered a wide range of biologic behaviour, from a slowly growing lesion already apparent at birth, to anaplastic astrocytoma in a young adult and glioblastomas at the age of less than 10 years. The only non-neural neoplasms in this family were a case of leukemia and an adrenocortical carcinoma. A germline deletion of codon 236 of the p53 tumour suppressor gene was identified as an underlying cause and detected in all affected family members. This mutation has not previously been reported as germline transmission or in sporadic tumours. The unusual accumulation of CNS tumours may be due to a certain organ-specific effect of this particular p53 mutation or it may reflect the specific genetic back-ground of this family.