Abstract

Mosaicism constitutes a frequent complication of the genotype–phenotype relationship in genetic disease and is an important consideration for the estimation of transmission risk. Mosaicism has been identified in several hereditary cancer syndromes including retinoblastoma, familial adenomatous polyposis coli, von Hippel–Lindau disease and neurofibromatosis type 2. Recent data support the postulate that the frequency of mosaicism is increased in cancer predisposition syndromes characterised by high new mutation rates. Since the new mutation rate is very high in neurofibromatosis type 1 (NF1), mosaicism might reasonably be expected to be frequent among sporadic cases but this remains to be formally demonstrated. Here we summarise current knowledge of mosaicism in NF1, focusing on the types of mutations identified as well as their inferred developmental timing and representation in different cell types, and assess the potential impact of high frequency mosaicism on mutation screening in patients with apparent de novo NF1.