CFTR and cystic fibrosis: Whereas the presence of two highly deleterious (‘severe’) CFTR alleles (as in p.F508del homozygotes) is necessary to give rise to classic cystic fibrosis, heterozygosity for such an allele is sufficient to confer an increased risk of ICP, whilst compound heterozygosity, involving a severe CFTR allele plus a less deleterious (‘mild’) allele (e.g. p. F508del/p.R117H), confers a further increase in risk [7,8].