Author:

Keywords:

nucleotide-binding fold, frameshift mutations, identification, delta-f508, variants, Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, NUCLEOTIDE-BINDING FOLD, FRAMESHIFT MUTATIONS, IDENTIFICATION, DELTA-F508, VARIANTS, Base Sequence, Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, Gene Expression, Haplotypes, Humans, Incidence, Membrane Proteins, Molecular Sequence Data, Mutation, 0604 Genetics, 1104 Complementary and Alternative Medicine, 1114 Paediatrics and Reproductive Medicine, 3105 Genetics, 3215 Reproductive medicine

Abstract:

The N1303K mutation was identified in the second nucleotide binding fold of the cystic fibrosis (CF) gene last year. We have gathered data from laboratories throughout Europe and the United States of America in order to estimate its frequency and to attempt to characterise the clinical manifestations of this mutation. N1303K, identified on 216 of nearly 15000 CF chromosomes tested, accounts for 1.5% of all CF chromosomes. The frequency of the N1303K allele varies significantly between countries and ethnic groups, being more common in Southern than in Northern Europe. This variation is independent of the DELTA-F508 allele. It was not found on UK Asian, American Black or Australian chromosomes. N1303K is associated with four different linked marker haplotypes for the polymorphic markers XV-2c, KM.19 and pMP6d-9. Ten patients are homozygous for this mutation, whereas 106 of the remainder carry one of 12 known CF mutations in the other CF allele. We classify N1303K as a "severe" mutation with respect to the pancreas, but can find no correlation between this mutation, in either the homozygous or heterozygous state, and the severity of lung disease.