Cis versus trans compound heterozygotes in cystic fibrosis

As CF is a recessive condition, abnormalities must be present in both CFTR alleles in order to cause disease. If the patient is homozygous for a mutation or pathogenic variant (eg, F508del), the variant appears in each of the two CFTR alleles and the individual will be affected (ie, CF or a CF-related disease). However, if genetic testing reveals two or more variants at different positions within the gene (so-called compound heterozygote), each CFTR allele (chromosome) could have one of the variants (in "trans," individual potentially affected) or both variants could be on the same allele (chromosome) and the other allele (chromosome) could be normal (in "cis," CF carrier). Genetic counseling with further testing (eg, genotyping the variants in informative relatives, ideally both parents) can help distinguish between these two scenarios.