Mosaic neurofibromatosis type 1 (mNF1), caused by postzygotic NF1 alterations, is characterized by localized or generalized NF1-related lesions such as café-au-lait macules (CMs) and plexiform neurofibroma (PNF). A giant CM (GCM) is sometimes seen in patients with NF1 but coexistence of GCM and melanocytic nevi is very rare. Here we report a case of mNF1 with peculiar manifestations: a GCM with melanocytic nevi and PNF. For genetic analyses, exome sequencing, RT-PCR/sequencing, multiplex ligation-dependent probe amplification (MLPA), TaqMan copy number assay were performed. The patient was an 8-year-old girl with a GCM that covered one third of her trunk and associated with multiple melanocytic nevi and PNF. The patient had no other NF1-related lesions except for five small CMs. Neither exome sequencing of the blood and PNF nor RT-PCR/sequencing of the blood detected NF1 mutations. MLPA detected no NF1 aberrations in the blood but did two NF1 microdeletions in the PNF: complete loss of one allele and an intragenic deletion affecting exons 25-30. Furthermore, to explore mechanisms of nevus development, nevus cells collected by microdissection were analyzed. MLPA and TaqMan copy number assay detected NF1 deletions similar to those found in PNF. Exome sequencing of the nevi detected no mutations related to nevogenesis. In conclusion, the patient was given a diagnosis of mNF1 caused by biallelic NF1 deletions. The deletions might be related to the nevus development but it was unknown whether unidentified genetic aberrations were also responsible.

Giant café-au-lait macule, plexiform neurofibroma and multiple melanocytic nevi in a patient with mosaic neurofibromatosis type 1 caused by biallelic NF1 microdeletions