Variable levels of normal RNA in different fetal organs carrying a cystic fibrosis transmembrane conductance regulator splicing mutation.

Journal Article (Journal Article)

Disease severity varies among cystic fibrosis (CF) patients carrying the same cystic fibrosis transmembrane conductance regulator (CFTR) genotype and among organs of the same individual. It has been shown that the class V splicing mutation 3849 + 10 kb C--> T produces both normal and aberrantly spliced CFTR transcripts. We analyzed the levels of normal CFTR messenger RNA (mRNA) in different organs of an aborted fetus carrying the 3849 + 10 kb C--> T mutation, and found that they correlated with the histopathologic changes observed in these organs. We performed semiquantitative nondifferential reverse transcription-polymerase chain reaction on several organs from a 22-wk aborted CF fetus carrying the 3849 + 10 kb C--> T mutation. A very low level (1%) of normal CFTR mRNA was detected in the severely affected ileum of this fetus. Higher levels were found in the histopathologically unaffected trachea (17%), colon (19%), and lung (26%). Thus, as early as in utero, the regulation of alternative splice-site selection is an important mechanism underlying variable CF severity. Understanding of the mechanisms regulating alternative splicing in different tissues will contribute to potential therapy for patients carrying splicing mutations in CF and other human disease genes.

Full Text

Duke Authors

Cited Authors

  • Chiba-Falek, O; Parad, RB; Kerem, E; Kerem, B

Published Date

  • June 1999

Published In

Volume / Issue

  • 159 / 6

Start / End Page

  • 1998 - 2002

PubMed ID

  • 10351951

International Standard Serial Number (ISSN)

  • 1073-449X

Digital Object Identifier (DOI)

  • 10.1164/ajrccm.159.6.9808012


  • eng

Conference Location

  • United States