Identification of the NF1 gene mutation in Korean families with neurofibromatosis type 1

Neurofibromatosis type 1 (NF1), the autosomal dominant diseases in humans, is caused by defects in the NF1 tumor-suppressor gene. To date, more than 700 independent mutations have been identified in the NF1 gene, the majority of which are family specific. The aim of this study was to investigate the pathogenic mutations in NF1 gene in 15 Korean NF1 families. We performed genetic analysis on 37 patients from 15 unrelated families by using RT-PCR and mRNA sequencing with 12 primer set including whole coding region of the NF1 gene. Here, we identified the familial and sporadic mutations in 34 of 37 patients (91.9 %) and found the familial mutations in 11 of 15 families (73.3 %). We detected 29 mutations of NF1 gene, which may encode the truncated form of neurofibromin. Four mutations were found in the cAMP-dependent protein kinase recognition sites (G1610A, c.2179delCAG) and the GTPase activating protein related domain (c.3169insT, c.2863delC). In this series of familial studies, we report a wide spectrum of NF1 mutations in Korean patients. We conclude that most mutations caused abnormal transcripts and premature termination of the mutant alleles. Then we suggest that these may provide further insights into the pathogenesis of NF1.