Skip to main content

Alternative splicing: a mechanism for phenotypic rescue of a common inherited defect.

Publication ,  Journal Article
Morisaki, H; Morisaki, T; Newby, LK; Holmes, EW
Published in: J Clin Invest
May 1993

Approximately 2% of Caucasians and African-Americans are homozygous for a nonsense mutation in exon 2 of the AMPD1 (AMP deaminase) gene. These individuals have a high grade deficiency of AMPD activity in their skeletal muscle. More than 100 patients with AMPD1 deficiency have been reported to have symptoms of a metabolic myopathy, but it is apparent many individuals with this inherited defect are asymptomatic given the prevalence of this mutant. Results of the present study provide a potential molecular explanation for "correction" of this genetic defect. Alternative splicing eliminates exon 2 in 0.6-2% of AMPD1 mRNA transcripts in adult skeletal muscle. Expression studies document that AMPD1 mRNA, which has exon 2 deleted, encodes a functional AMPD peptide. A much higher percentage of alternatively spliced transcripts are found during differentiation of human myocytes in vitro. Transfection studies with human minigene constructs demonstrate that alternative splicing of the primary transcript of human AMPD1 is controlled by tissue-specific and stage-specific signals. Alternative splicing of exon 2 in individuals who have inherited this defect provides a mechanism for phenotypic rescue and variations in splicing patterns may contribute to the variability in clinical symptoms.

Duke Scholars

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

May 1993

Volume

91

Issue

5

Start / End Page

2275 / 2280

Location

United States

Related Subject Headings

  • White People
  • Transfection
  • Transcription, Genetic
  • Sequence Deletion
  • Recombinant Proteins
  • RNA, Messenger
  • Promoter Regions, Genetic
  • Polymerase Chain Reaction
  • Phenotype
  • Oligodeoxyribonucleotides
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Morisaki, H., Morisaki, T., Newby, L. K., & Holmes, E. W. (1993). Alternative splicing: a mechanism for phenotypic rescue of a common inherited defect. J Clin Invest, 91(5), 2275–2280. https://doi.org/10.1172/JCI116455
Morisaki, H., T. Morisaki, L. K. Newby, and E. W. Holmes. “Alternative splicing: a mechanism for phenotypic rescue of a common inherited defect.J Clin Invest 91, no. 5 (May 1993): 2275–80. https://doi.org/10.1172/JCI116455.
Morisaki H, Morisaki T, Newby LK, Holmes EW. Alternative splicing: a mechanism for phenotypic rescue of a common inherited defect. J Clin Invest. 1993 May;91(5):2275–80.
Morisaki, H., et al. “Alternative splicing: a mechanism for phenotypic rescue of a common inherited defect.J Clin Invest, vol. 91, no. 5, May 1993, pp. 2275–80. Pubmed, doi:10.1172/JCI116455.
Morisaki H, Morisaki T, Newby LK, Holmes EW. Alternative splicing: a mechanism for phenotypic rescue of a common inherited defect. J Clin Invest. 1993 May;91(5):2275–2280.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

May 1993

Volume

91

Issue

5

Start / End Page

2275 / 2280

Location

United States

Related Subject Headings

  • White People
  • Transfection
  • Transcription, Genetic
  • Sequence Deletion
  • Recombinant Proteins
  • RNA, Messenger
  • Promoter Regions, Genetic
  • Polymerase Chain Reaction
  • Phenotype
  • Oligodeoxyribonucleotides