Analysing tumours for genetic diagnosis in mosaic neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is an autosomal dominantly inherited disorder caused by pathogenic variants in the NF1 gene, resulting in diverse clinical manifestations, especially multiple cutaneous neurofibromas. In approximately 50% of cases, variants occur de novo, and a portion of these cases involves genetic mosaicism, where variants are present in a subset of cells of an individual. Mosaic NF1 often presents with a milder phenotype and reduced transmission risk, complicating clinical diagnosis and genetic consulting. Conventional blood-based genetic testing may fail to detect the pathogenic variants in mosaic cases, necessitating additional analysis using tumour-derived DNA. We present five such cases and suggest a comprehensive diagnostic workflow focusing on tumour-based analysis for mosaic cases.