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

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.