Exon 10b of the NF1 gene represents a mutational hotspot and harbors a recurrent missense mutation Y489C associated with aberrant splicing

Genet Med. 1999 Sep-Oct;1(6):248-53. doi: 10.1097/00125817-199909000-00002.

Abstract

Purpose: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • DNA, Complementary / metabolism
  • Exons
  • Female
  • Humans
  • Male
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation, Missense*
  • Nerve Tissue Proteins / genetics*
  • Neurofibromin 1
  • Open Reading Frames
  • Polymorphism, Genetic
  • Protein Biosynthesis
  • RNA Splicing*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic

Substances

  • DNA, Complementary
  • Nerve Tissue Proteins
  • Neurofibromin 1

Associated data

  • GENBANK/AC004222
  • GENBANK/AF064564
  • GENBANK/D45201
  • GENBANK/L10370
  • GENBANK/L26501