PMID: 8950674Nov 1, 1996Paper

Splicing mutations in DMD/BMD detected by RT-PCR/PTT: detection of a 19AA insertion in the cysteine rich domain of dystrophin compatible with BMD

Journal of Medical Genetics
P A RoestJ T den Dunnen

Abstract

We have used an RNA based mutation detection method to screen the total coding region of the dystrophin gene of a Duchenne and a Becker muscular dystrophy patient in whom DNA based mutation detection methods have so far failed to detect mutations. By RT-PCR and the protein truncation test (PTT) we could identify point mutations in both cases. DMD patient DL184.3 has a T-->A mutation in intron 59 at position -9, creating a novel splice acceptor site for exon 60. As a result seven intronic bases are spliced into the mRNA, causing a frameshift and premature translation termination 20 codons downstream. Since this patient had died and only fibroblasts were available, we applied MyoD induced myodifferentiation of stored fibroblasts to enhance muscle specific gene expression. With the results of this mutation analysis, prenatal diagnosis could subsequently be performed in this family. BMD patient BL207.1 carries a G-->C mutation at position +5 of intron 64, disrupting the splice donor consensus sequence and activating a cryptic splice donor site 57bp downstream. The inclusion of these 57 intronic bases in the mRNA leaves the reading frame open and results in the insertion of 19 amino acids into the cysteine rich domain of dystrophin....Continue Reading

References

Oct 1, 1992·Human Molecular Genetics·V NigroG A Puca
Jun 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·D LederfeinU Nudel
Mar 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·R G RobertsD R Bentley
Nov 1, 1990·Human Genetics·A H BeggsL M Kunkel
Dec 9, 1988·Nucleic Acids Research·J S ChamberlainC T Caskey
Jan 1, 1993·Human Molecular Genetics·R G RobertsM Zatz
Mar 1, 1995·Human Molecular Genetics·H G LidovL M Kunkel
Mar 1, 1994·American Journal of Medical Genetics·T W PriorJ R Mendell
Oct 1, 1993·Human Molecular Genetics·P A RoestJ T den Dunnen
May 1, 1993·Nature Genetics·T J ByersL M Kunkel

❮ Previous
Next ❯

Citations

Oct 25, 2003·Nucleic Acids Research·Xavier RocaAdrian R Krainer
Sep 6, 2005·Nucleic Acids Research·Jana KrálovicováIgor Vorechovský
Oct 6, 2005·Biosensors & Bioelectronics·Hyun Gyu ParkNam Huh
Jun 19, 2019·Annals of Clinical and Translational Neurology·Layal AntouryThurman M Wheeler

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.