IDENTIFICATION OF A SPLICE-SITE MUTATION (2789-G-GREATER-THAN-A) ASSOCIATED WITH SMALL AMOUNTS OF NORMAL CFTR MESSENGER-RNA AND MILD CYSTIC-FIBROSIS(5)

A splicing mutation was identified at the 1-5 position of the splice d onor site of exon 14b of CFTR in CF patients in a consanguineous famil y that is remarkable for unusually mild disease. Quantitative studies of nasal epithelial mRNA revealed that homozygotes for the spice site mutation produced approximately 4% of the normal amount of normally-sp liced CFTR. We propose that this small amount of normally spliced mRNA is associated with synthesis of some normal CFTR protein, and account s for the mild phenotype, Further characterization of epithelial funct ion and clinical phenotype in patients bearing this form of mutation, termed a type V mutation, will be useful in determining the level of C FTR associated with amelioration of lung disease. (C) 1997 Wiley-Liss, Inc.