Apparent homozygosity of a novel frame shift mutation in the CFTR gene because of a large deletion.

Patients develop cystic fibrosis because of a variety of homozygous recessive mutations, including single nucleotide polymorphisms, insertions, and deletions, in the cystic fibrosis transmembrane regulator (CFTR) gene, or because of compound heterozygosity for two mutations in the CFTR gene. A false determination of homozygosity for a particular CFTR mutation could negatively affect both carrier screens for a patient's family as well as researchers' ability to study the physiological implications of a particular mutation. We argued previously that homozygosity for rare or novel mutations in the CFTR gene could result from a mutation on one allele and the presence of a large deletion encompassing the same sequence region on the second allele. We present here a patient with classic cystic fibrosis who has a novel microdeletion in exon 7 on one allele and a large deletion encompassing exon 7 on the second allele. These data highlight the need to prevent misdiagnosis of homozygous mutations, which can lead to misinterpretation of mutation penetrance and its effects on protein function.