Distinguishing Homozygous and Heterozygous Cystic Fibrosis Fibroblasts from Normal Cells by Differences in Sodium Transport

Abstract

We have found that cultured fibroblasts from patients with cystic fibrosis (CF) accumulate less ²²Na in the presence of ouabain than do normal cells. After equilibration with ²²Na, the ratio of cell-associated ²²Na in ouabain-exposed cells to that in unexposed cells, after five hours of incubation, was 2.34±0.14 (mean ±S.D.) in 13 fibroblast strains from normal subjects and 1.33±0.08 in eight strains from patients with CF. Cells from eight different obligate CF heterozygotes (parents of children with CF) had a ratio of 1.38±0.07; those from three unaffected siblings (who have a two-thirds chance of carrying the disease) had a ratio of 1.27±0.04. The differences between CF homozygotes or heterozygotes and normal subjects were highly significant (P<0.001), but there was considerable overlap between CF homozygotes and heterozygotes. This abnormality of sodium transport provides an unequivocal in vitro test that distinguishes normal cells from cells derived from CF homozygotes or heterozygotes. It should be useful for the identification of carriers of the CF gene. (N Engl J Med. 1981; 304:1–5.)