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Somatic Cell and Molecular Genetics

, Volume 22, Issue 2, pp 145–150 | Cite as

Germinal HPRT splice donor site mutation results in multiple RNA splicing products in T-lymphocyte cultures

  • T. C. Hunter
  • S. B. Melancon
  • L. Dallaire
  • S. Taft
  • T. R. Skopek
  • R. J. Albertini
  • J. P. O'Neill
Article

Abstract

We have used peripheral blood T-lymphocyte cultures to analyze the hprt mutation in two Lesch-Nyhan syndrome males who are cousins and to confirm the carrier status of female members of the family. Both cDNA and genomic DNA sequencing studies show that this patient carries a hitherto undescribed single base deletion in the exon 5 donor splice site sequence (15:+1, δG, base number 31635). The largest cDNA product contained all nine hprt exons plus an insertion of 66 bases of intron 5, consistent with the use of a cryptic splice site in intron 5 (aag67/gtaagc). This splicing error would result in a chain terminating codon immediately after exon 5 (15:2–4, taa) and predicts a polypeptide of 133 amino acids. This loss of the normal splice donor site also results in multiple hprt mRNA species, combining the use of the cryptic splice site in intron 5 and splicing errors involving exons 2–6. In addition to defining a new Lesch-Nyhan mutation (hprtHenryville), these results provide insight into aberrant splicing of hprt mRNA in T-lymphocytes.

Keywords

Splice Donor Site Aberrant Splice Splice Product Cryptic Splice Site Base Deletion 
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.

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Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • T. C. Hunter
    • 1
  • S. B. Melancon
    • 2
  • L. Dallaire
    • 2
  • S. Taft
    • 3
  • T. R. Skopek
    • 3
  • R. J. Albertini
    • 1
  • J. P. O'Neill
    • 1
  1. 1.University of Vermont Genetics LaboratoryBurlington
  2. 2.Génétique Médicale Centre de Recherche Pédiatrique, Hôpital Sainte-JustineUniversité de MontréalQuébecMontréalCanada
  3. 3.University of North CarolinaCarolinaChapel Hill, North

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