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Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder
affecting one in 3,500 individuals. The mutation rate in the NF1 gene
is one of the highest known for human genes. Compared to other methods,
the protein truncation test (PTT) provides improved efficiency in detecting
NF1 mutations which are dispersed throughout the gene which spans 350
kilobases of genomic DNA. We have applied the PTT and subsequent
sequence analysis of cloned cDNA to identify mutations in NF1 patients.
We report here the identification of two novel (W336X and Q315X),
and one recurrent (R304X) mutation located in exon 7 and show that
all three premature termination codons lead to skipping of exon 7 in
a proportion of the transcripts derived from the mutated allele.
Possible mutation-induced alterations of the RNA secondary structure
and their impact on skipping of exon 7 of the NF1 gene are explored
and discussed.
Keywords: NF1, neurofibromatosis type I, mutation, exon skipping, RNA secondary structure
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