[Identification of a mosaic mutation of NF1 gene in a sporadic case of neurofibromatosis type 1].

Objective: To detect NF1 gene mutation in a patient with neurofibromatosis type 1.

Methods: Five fragments encompassing the entire coding sequence of the NF1 gene were amplified with reverse transcription PCR. PCR products were directly sequenced. Suspected mutations were verified by sequencing of DNA amplified by PCR using genomic DNA as template. Corresponding exon of family members was also sequenced. Furthermore, the PCR products were inserted into a pGEM-T cloning vector to quantify cells carrying the mutation in different samples derived from the three embryonic layers.

Results: The proband's clinical manifestation was consistent with neurofibromatosis type 1. Sequence analysis has identified a novel heterozygous mutation c.7911 C to T (p.Q2510X) in exon 51 of the NF1 gene in the proband. The same mutation was also detected in peripheral blood cells, uroepithelial cells and oral mucosal cells of the proband, though the signals of uroepithelial cells were significantly weaker. By T cloning-sequencing, recombinants carrying the NF1 gene mutation respectively accounted for 42%, 36% and 12% of all peripheral blood cells, oral mucosal cells and uroepithelial cells .

Conclusion: It is likely that a mutation of NF1 gene has occurred in early embryogenesis of the proband, which in turn has led to generalized mosaicism of neurofibromatosis type 1.