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Human Genetics

, Volume 113, Issue 6, pp 551–554 | Cite as

NF1 exon 7 skipping and sequence alterations in exonic splice enhancers (ESEs) in a neurofibromatosis 1 patient

  • Patrizia Colapietro
  • Cristina Gervasini
  • Federica Natacci
  • Livia Rossi
  • Paola Riva
  • Lidia LarizzaEmail author
Short Report

Abstract

The underestimates of NF1 gene mutations in neurofibromatosis 1 (NF1) have been attributed to the large size of the NF1 gene, the considerable frequency of gross deletions and the common occurrence of splicing defects that are only detectable by cDNA analysis. We here report on a patient with severe NF1 showing at RT-PCR analysis the expected fragment from exon 4b to 8 together with a shortened one with the in-frame skipping of exon 7. Sequencing of the corresponding genomic fragment revealed a G→A transition and a C→A transversion at nucleotide positions 57 and 58 of the 174-bp long exon 7, neither of which was present in the proband's parents or 50 healthy controls. No other variation was found in the entire NF1 coding sequence. The use of previously established sequence matrices for the scoring of putative ESE motifs showed that the adjacent silent and missense mutations are located within highly conserved overlapping stretches of seven nucleotides with a close similarity to the ESE-specific consensus sequences recognised by the SC35 and SF2/ASF SR proteins. The combined occurrence of both consecutive alterations decreases the motif score for both SF2/ASF and SC35 below their threshold levels. As the aberrant transcript is consistently expressed, a protein lacking 58 amino acids is predicted. Thus the contiguous internal exon 7 mutations are suggested to cause exon 7 skipping as a result of the mis-splicing caused by abrogation of functional ESEs.

Keywords

Exonic Splice Enhancer Aberrant Transcript Exonic Splice Enhancer Motif Putative Exonic Splice Enhancer Occipitofrontal Head Circumference 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

We thank the family that participated in this study. This work was supported by a grant from Italian Ministry of Health on neurofibromatosis 1 and by a 2002 AIRC (Associazione Italiana per la Ricerca sul Cancro) grant (to L.L.) and a 2002 FIRST grant (to P.R).

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Patrizia Colapietro
    • 1
  • Cristina Gervasini
    • 1
  • Federica Natacci
    • 2
  • Livia Rossi
    • 3
  • Paola Riva
    • 1
  • Lidia Larizza
    • 1
    Email author
  1. 1.Department of Biology and Genetics for Medical SciencesUniversity of MilanMilanItaly
  2. 2.Medical Genetics ServiceIstituti Clinici di PerfezionamentoMilanItaly
  3. 3.II Pediatrics DepartmentMilanItaly

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