Germinal HPRT splice donor site mutation results in multiple RNA splicing products in T-lymphocyte cultures
Autor: | Richard J. Albertini, S. Taft, T. R. Skopek, S. B. Melancon, L. Dallaire, J.P. O'Neill, T. C. Hunter |
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Rok vydání: | 1996 |
Předmět: |
Male
Hypoxanthine Phosphoribosyltransferase DNA Complementary Lesch-Nyhan Syndrome RNA Splicing T-Lymphocytes DNA Mutational Analysis Molecular Sequence Data Exonic splicing enhancer Biology medicine.disease_cause Exon Complementary DNA Genetics medicine Humans Child Cells Cultured Sequence Deletion Mutation Splice site mutation Base Sequence Genetic Carrier Screening Intron Infant Cell Biology General Medicine DNA Exons Molecular biology genomic DNA RNA splicing Female |
Zdroj: | Somatic cell and molecular genetics. 22(2) |
ISSN: | 0740-7750 |
Popis: | 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 (I5: +1, delta G, 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 (I5:2-4, 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. |
Databáze: | OpenAIRE |
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