Mutation spectrum of NF1 gene in Italian patients with neurofibromatosis type 1 using Ion Torrent PGM™ platform

Neurofibromatosis type 1 (NF1) is caused by mutations of the NF1 gene and is one of the most commonhuman autosomal dominant disorders. The patient shows different signs on the skin and other organsfrom early childhood. The best known are six or more cafe au lait spots, axillary or inguinal freckling,increased risk of developing benign nerve sheath tumours and plexiform neurofibromas. Mutationdetection is complex, due to the large gene size, the large variety of mutations and the presence ofpseudogenes. Using Ion Torrent PGM™ Platform, 73 mutations were identified in 79 NF1 Italian patients,51% of which turned out to be novel mutations. Pathogenic status of each variant was classified using“American College of Medical Genetics and Genomics” guidelines criteria, thus enabling the classificationof 96% of the variants identified as being pathogenic. The use of Next Generation Sequencing has provento be effective as for costs, and time for analysis, and it allowed us to identify a patient with NF1mosaicism. Furthermore, we designed a new approach aimed to quantify the mosaicism percentageusing electropherogram of capillary electrophoresis performed on Sanger method.