564 W.-J. Koh, C.-S. Ki, J.-W. Kim, et al. A B Fig. 1. Chest plain radiograph shows diffuse reticulonodular densities in both central lung areas with symmetricity (A). A tram tract sign is noted in right middle lung zone, representing bronchiectasis. On computed tomographic image with lung window setting, diffuse bronchiec- tasis and bronchiolectasis are seen in both lungs with ill-defined small centrilobular nodules, representing associated bronchiolitis. Under- lying lung parenchyme is hyperlucent due to air-trapping (B). Q98R/- -/Q220X Q98R/- -/- Q98R/Q220X Fig. 2. Pedigree of a Korean family with cystic fibrosis. A heterozy- gous Q98R mutation is found in the father, brother, and the proband, and another heterozygous Q220X mutation is found in the mother and the proband. Squares indicate males, circles indicate females, and an arrow indicates the proband. Open symbols with or with- out central dot indicate carriers and an unaffected family mem- ber, respectively, and a darkened symbol indicates an affected family member. rial administration, revealed bilateral multifocal bronchiec- tasis and multiple centrilobular nodules (Fig. 1). Pulmonary function studies showed a forced vital capacity of 2.62 L (63% of predicted), with a forced expiratory volume of 1.36 L per second (36% of predicted). The patient’s total lung capacity was measured to be 6.39 L (121% of predicted). A CT scan of his paranasal sinuses evidenced severe inflammatory changes, associated with pansinusitis. Staphylococcus aureus was cultured from his sputum. Mycobacterial and fungal cultures were negative. A tuberculin skin test was also negative. Condi- tions such as immunodeficiency and ciliary dyskinesia were ruled out by the normal results of serum immunoglobulin tests, and by the finding of normal bronchial mucosal biop- sy. There was no evidence of exocrine pancreatic insufficien- cy and malaborption. The sweat chloride concentration was measured by a quan- titative pilocarpine iontophoresis sweat test, in accordance with the guidelines of the National Committee for Clinical Laboratory Standards (7). The average sweat chloride concen- trations on both forearms were 63.0 mM/L, a finding that exceeded the reference limit (<40 mM/L). Direct sequencing analysis of all coding exons and their flanking intronic sequences demonstrated that the patient possessed two mutations in his CFTR gene (Fig. 2): a het- erozygous A to G transition in exon 4 (c.293A>G; Q98R) and a heterozygous C to T transition in exon 6a (c.658C>T; Q220X). A family study demonstrated that the patient’s father and elder brother both also possessed the Q98R muta- tion, whereas his mother harbored the Q220X mutation. The patient’s sister, however, harbored no such mutations. Based on our search of the Cystic Fibrosis Mutation Database (http://www.genet.sickkids.on.ca/cftr/), Q98R and Q220X mutations have been reported in CF patients from Southern France and Southern England (8, 9). DISCUSSION CF is the most frequently encountered life-limiting auto- somal recessive genetic disorder in Caucasians, with an inci-