ECL, extracellular loop; F, female; M, male; NA, not available; NBD, nucleotide-binding domain; TMD, trans-membrane domain. Cystic Fibrosis with CFTR Gene Mutations Table 1. Summary of the CFTR gene mutations identified in Korean Mutation Nucleotide change Exon CFTR domain Ethnicity L88X Q98R R117H I125T K166E E217G Q220X IVS8 T5 delF508 I556V Q1291X Q1352H R1453W c.263T>G c.293A>G c.350G>A c.374T>C c.496A>G c.650A>G c.658C>T - c.1522_1524delTTT c.1666A>G c.3871C>T c.4056G>C c.4357C>T 3 4 4 4 5 6a 6a - 10 11 20 22 24 TMD1 TMD1 ECL1 TMD1 TMD1 ECL2 ECL2 - NBD1 NBD1 NBD2 NBD2 C-terminal Korean-Caucasian Native Korean Native Korean Native Korean Korean-Caucasian Native Korean Native Korean Native Korean Native Korean Native Korean Native Korean Native Korean Native Korean dence of 1 in every 3,200 newborns in the United States (1). However, it is less common in African Americans (1 in 15,000) (10) and quite rare in Asians (1 in 350,000 in the Japanese population) (2, 3). CF is normally suspected upon the finding of one or more typical CF phenotypical features, including chronic sinopulmonary disease, gastrointestinal/ nutritional abnormalities, salt loss syndrome, and obstruc- tive azoospermia in males (7). CF is caused by mutations in the CFTR gene, which is located on the long arm of chromosome 7. This gene consists of 27 exons, and encodes for an integral membrane protein composed of 1,480 amino acids. Functionally, CFTR regu- lates the expression of the chloride (Cl-) channel, which is expressed in the apical membrane of exocrine epithelial cells (1). Currently, approximately 1,366 mutations and polymor- phisms are listed in the Cystic Fibrosis Mutation Database (http://www.genet.sickkids.on.ca/cftr/). However, only 11 mutations have been reported in the Korean population thus far (Table 1). In the present study, we report two additional mutations in the list of CFTR gene mutations (Q98R and Q220X), which have been identified in Koreans. It is of note that these two mutations have previously been reported in CF patients from Southern France (8) and Southern England (9), respectively, but are not frequently encountered muta- tions even in the Caucasian population. As shown in the Table, no mutation except IVS8 T5 vari- ant has repeatedly been observed in Korean population. Fur- thermore, only two mutations (R117H and delF508) are found among 25 mutations in the screening panel for Cau- casian CF patients recommended by the American College of Medical Genetics (11). Therefore, as demonstrated by Lee et al. (12), a possible common mutation might not exist in the Korean population. Although CF tends to be discovered early in life, the diagno- sis of CF is being made in adults with increased frequency (13, 14). Patients diagnosed as adults normally present with Sex M M F M F F Age (yr) at diagnosis 0.1 15 10 15 27 9 Diagnosis Meconium ileus Cystic fibrosis Control Control Cystic fibrosis Bronchiectasis Cystic fibrosis Bronchiectasis Bronchoalveolar carcinoma Control, bronchiectasis Cystic fibrosis Bronchiectasis, pancreatitis Control, bronchiectasis 565 Reference (15) Present study (12) (12) (16) (12) Present study (4, 12) (17) (12) (4) (12) (12) chronic respiratory problems. As a group, they exhibit a milder variant of lung disease, a lesser degree of Pseudomonas infection, and are more likely to be pancreatic-sufficient than are patients in whom CF is diagnosed at earlier ages (13, 14). Physicians who are unfamiliar with the spectrum of CF phenotypic mani- festations may not consider CF as a component of their dif- ferential diagnoses, thus delaying accurate diagnosis. In summary, we report here a Korean CF patient, who was diagnosed via a sweat chloride test, as well as a molecular genetic analysis of the patient’s CFTR gene. Although CF continues to be quite a rare condition in Koreans, CF should still be suspected in patients exhibiting recurrent and unex- plained chronic respiratory symptoms. REFERENCES 1. Welsh MJ, Ramsey BW, Accurso F, Cutting GR. Cystic fibrosis. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular basis of inherited disease. 8th ed. New York: McGraw- Hill; 2001: 5121-88. 2. Imaizumi Y. Incidence and mortality rates of cystic fibrosis in Japan, 1969-1992. Am J Med Genet 1995; 58: 161-8. 3. Yamashiro Y, Shimizu T, Oguchi S, Shioya T, Nagata S, Ohtsuka Y. The estimated incidence of cystic fibrosis in Japan. J Pediatr Gas- troenterol Nutr 1997; 24: 544-7. 4. Ahn KM, Park HY, Lee JH, Lee MG, Kim JH, Kang IJ, Lee SI. Cys- tic fibrosis in Korean children:a case report identified by a quanti- tative pilocarpine iontophoresis sweat test and genetic analysis. J Korean Med Sci 2005; 20: 153-7. 5. Moon HR, Ko TS, Ko YY, Choi JH, Kim YC. Cystic fibrosis-a case presented with recurrent bronchiolitis in infancy in a Korean male infant. J Korean Med Sci 1988; 3: 157-62. 6. Park SH, Lee HJ, Kim JH, Park CH. Cystic firbosis: case report. J Korean Radiol Soc 2002; 47: 693-6. 7. Rosenstein BJ, Cutting GR. The diagnosis of cystic fibrosis: a con-