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