Neurofibromatosis type 2 discordance in monozygous twins

AbstractNeurofibromatosis type 2 (NF2) is an autosomal dominant condition caused by pathogenic variants in theNF2 gene. The pathogenic variant is either inherited or obtained by de novo mutation, characterised by the presence of schwannomas, meningiomas and ependymomas. Here we report the presence ofNF2 in one twin, with bilateral vestibular schwannomas and a pathogenic variant of theNF2 gene identified in both tumour and lymphocytes, while his monozygous brother remains asymptomatic. Imaging of the unaffected twin showed no tumour load and genetic testing via Sanger sequencing and Amplification Refractory Mutation System assay demonstrated low levels of expression of the NF2 variant in lymphocytes. Further testing on non-haemopoietic tissue showed little expression or absence of the pathogenic variant. Given there is no family history and the low level of the variant, we assume the pathogenic variant is a de novo mutation during embryogenesis. De novo mutations have been described as occurring at three possible time points in the creation of monozygous twins with different genetic make-up; prior to the twinning event, as a cause of the event, or after the twinning event. Of these options, we hypothesise that the discordance in the expression of theNF2 variant between these twins is likely due to a mutational event that occurred as a result of either of the latter two possibilities, between which we cannot determine. The pathogenic variant in lymphocytes was likely transferre...

Source: Familial Cancer - January 20, 2020 Category: Cancer & Oncology Source Type: research