Exon 10b of the NF1 gene represents a mutational hotspot and harbors a recurrent missense mutation Y489C associated with aberrant splicing.
OBJECTIVE
To analyze the spectrum and frequency of NF1 mutations in exon 10b.


METHODS
Mutation and sequence analysis was performed at the DNA and cDNA level.


RESULTS
We identified nine exon 10b mutations in 232 unrelated patients. Some mutations were recurrent (Y489C and L508P), others were unique (1465-1466insC and IVS10b+2delTAAG). Surprisingly, at the RNA level, Y489C causes skipping of the last 62 nucleotides of exon 10b. Another recurrent mutation, L508P, is undetectable by the Protein Truncation Test.


CONCLUSIONS
As exon 10b shows the highest mutation rate yet found in any of the 60 NF1 exons, it should be implemented with priority in mutation analysis.
Department of Medical Genetics, University Hospital, Gent, Belgium.
L M
LM
Messiaen
T
T
Callens
K J
KJ
Roux
G R
GR
Mortier
A
A
De Paepe
M
M
Abramowicz
M A
MA
Pericak-Vance
J M
JM
Vance
M R
MR
Wallace
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008957:Models, Genetic; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D025542:Neurofibromin 1; D016366:Open Reading Frames; D011110:Polymorphism, Genetic; D014176:Protein Biosynthesis; D012326:RNA Splicing; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D025542:Neurofibromin 1