Neurofibromatosis type 1 (NF1) is a common cancer predisposition syndrome affecting the nervous system. The disease is one of the most common autosomal dominant diseases in all ethnic groups. Although the gene was mapped to human chromosome 17 and isolated in 1990, the detection of NF1 mutation is still considered to be a challenge as the gene is large and contains multiple exons. Here we report the detection of three genomic mutations in three Chinese patients living in Taiwan. A DNA diagnosis procedure was established to investigate the NF1 gene mutation at both the transcript and genomic DNA levels. Mutations causing transcript alteration were uncovered in three patients. In the first case, we detected a deletion involving exons 39-45 (nucleotide 7,260-8,167 in GenBank accession No. M89914). In the second case, a 2,199-2,448 deletion resulted in skipping of exon 13. The third case skipped the exon 3 in the mutant transcript. We further investigated what caused the cDNA deletion by PCR using genomic DNA as a template. In the first patient, we identified an approximately 17.5 kbp deletion in the NF1 gene. In the other two patients, we identified a single-base substitution (IVS13+1G>A) at the splicing donor site in the second case, and an IVS3+1G>T substitution in the third case. We conclude that genomic deletion and alteration of splicing signal caused abnormal transcripts and truncated proteins in the three Taiwanese NF1 cases.
