A recurrent deep-intronic splicing CF mutation emphasizes the importance of mRNA studies in clinical practice

J Cyst Fibros. 2011 Dec;10(6):479-82. doi: 10.1016/j.jcf.2011.06.011. Epub 2011 Jul 23.

Abstract

Background: The identification by CFTR mRNA studies of a new deep-intronic splicing mutation, c.870-1113_1110delGAAT, in one patient of our series with mild CF symptoms and in three CF patients of an Italian study, led us to evaluate the mutation frequency and phenotype/genotype correlations.

Methods: 266 patients with CF and related disorders and having at least one undetected mutation, were tested at the gDNA level in three French reference laboratories.

Results: In total, the mutation was found in 13 unrelated patients (5% of those already carrying a mutation) plus 4 siblings, including one homozygote and 12 heterozygotes having a severe CF mutation. The sweat test was positive in 10/14 documented cases, the diagnosis was delayed after 20 years in 9/15 and pancreatic insufficiency was present in 5/16.

Conclusion: c.870-1113_1110delGAAT should be considered as CF-causing with phenotype variability and overall delayed diagnosis. Its frequency highlights the potential of mRNA studies.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cystic Fibrosis / diagnosis
  • Cystic Fibrosis / genetics*
  • Female
  • Humans
  • Infant, Newborn
  • Introns / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • RNA, Messenger / genetics*
  • Young Adult

Substances

  • RNA, Messenger