Fifty-four novel mutations in the NF1 gene and integrated analyses of the mutations that modulate splicing.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant genetic disorder caused by mutations in the NF1 gene. One of the hallmarks of NF1 is the high mutation rate in this gene. In this study, we present 127 different NF1 mutations and 54 novel mutations detected at both the genomic DNA and mRNA level using a retrospective case series review. We found that 25.2% of these different mutations induced aberrant splicing. Of note, 40.6% of these splicing errors were caused by exonic variants. In addition, one mutation produced mosaicism in the post-transcriptional profile. However, studies investigating these splicing aberrations are limited. In order to better understand the pathogenicity of NF1 and to provide a more accurate interpretation in molecular diagnostic testing, combined computational analyses were employed to elucidate the underlying mechanisms of the variants modulating NF1 gene splicing.