Pitfall in the use of genotype analysis as the sole diagnostic criterion for cystic fibrosis

In this report, we present an asymptomatic infant, seen for a second opinio n, who was given the diagnosis of cystic fibrosis (CF) as a neonate based o n the presence of two mutant alleles, Delta F508 and R117H. The diagnosis o f CF adversely affected the family's emotional, employment, and financial s tatuses. Our evaluation included sweat chloride, nasal transepithelial pote ntial difference, and bronchoscopy with bronchoalveolar lavage measurements , all which were consistent with findings expected from an individual witho ut CF. Genotype analysis for the sequence polymorphism in intron 8 of the c ystic fibrosis transmembrane conductance regulator (CFTR) gene revealed the 7 thymidines and 9 thymidines alleles. We conclude that this patient proba bly expresses enough epithelial cell surface CFTR function such that she ha s a normal phenotype. Based on our evaluation, she does not meet the curren t diagnostic criteria for CF. Although genotype analysis can be an useful a djunct, it should not be the sole diagnostic criterion for CF.