Mild cystic fibrosis linked to chromosome 7q22 markers with an uncommon haplotype

Cystic fibrosis is the commonest autosomal recessive genetic disorder among northern Europeans and their descendants. Recently, investigators have mapped the gene for cystic fibrosis to chromosome 7. We report the results of DNA linkage analysis in a consanguineous family with mild cystic fibrosis. The probes used in this study were pmet D, pmet H, XV-2c, KM.19, and pJ3.11. Linkage to the identified cystic fibrosis locus of 7q22 was established with a peak logarithm of the odds (lod) score of 3.00 at a recombination fraction Θ = 0.00 using the tightly linked marker KM.19. In addition, we found the D haplotype, which is not commonly associated with cystic fibrosis, to be segregating in this family. The D haplotype is composed of the 1.4-kb allele detectable by XV-2c and the 6.6-kb allele detectable by KM.19. The three patients with cystic fibrosis who had consanguineous parents were homozygous DD, were among the least severely affected, and had no pancreatic insufficiency. The five patients with unrelated parents were heterozygous for the D haplotype and the commoner B haplotype, except one patients who was homozygous DD. All affected persons with pancreatic insufficiency had the DB genotype. These DNA linkage studies provide additional evidence for the existence of a cystic fibrosis allele that is associated with mild disease.