A Novel Donor Splice Site in Intron 11 of the CFTR Gene, Created by Mutation 1811 +1.6kbA→G, Produces a New Exon: High Frequency in Spanish Cystic Fibrosis Chromosomes and Association with Severe Phenotype

M. Chillón, T. Dörk, T. Casals, J. Giménez, N. Fonknechten, K. Will, D. Ramos, V. Nunes, Xavier P. Estivill

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Abstract

mRNA analysis of the cystic fibrosis transmembrane regulator (CFTR) gene in tissues of cystic fibrosis (CF) patients has allowed us to detect a cryptic exon. The new exon involves 49 base pairs between exons 11 and 12 and is due to a point mutation (1811 + 1.6kbA→G) that creates a new donor splice site in intron 11. Semiquantitative mRNA analysis showed that 1811 + 1.6kbA→G-mRNA was 5-10-fold less abundant than ΔF508 mRNA. Mutation 1811 + 1.6kbA→G was found in 21 Spanish and 1 German CF chromosomes, making it the fourth-most-frequent mutation (2%) in the Spanish population. Individuals with genotype ΔF508/1811 + 1.6kbA→G have only 1%-3% of normal CFTR mRNA. This loss of 97% of normal CFTR mRNA must be responsible for the pancreatic insufficiency and for the severe CF phenotype in these patients.

Original languageEnglish
Pages (from-to)623-629
Number of pages7
JournalAmerican Journal of Human Genetics
Volume56
Issue number3
Publication statusPublished - 1995
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics

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