J Korean Med Sci.  2010 Jan;25(1):166-171. 10.3346/jkms.2010.25.1.166.

The L441P Mutation of Cystic Fibrosis Transmembrane conductance Regulator and its Molecular Pathogenic Mechanisms in a Korean Patient with Cystic Fibrosis

• Gee HY
• Kim CK
• Kim SW
• Lee JH
• Kim JH
• Kim KH
• Lee MG

• KMID: 1713852
• DOI: http://doi.org/10.3346/jkms.2010.25.1.166

Abstract

Cystic fibrosis (CF) is an autosomal recessive disorder usually found in populations of white Caucasian descent. CF is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. A 5-yr-old Korean girl was admitted complaining of coughing and greenish sputum. Chest radiographs and computed tomographic (CT) scan revealed diffuse bronchiectasis in both lungs. The patient had chronic diarrhea and poor weight gain, and the abdominal pancreaticobiliary CT scan revealed atrophy of the pancreas. Finally, CF was confirmed by the repeated analysis of the quantitative pilocarpine iontophoresis test. The chloride concentration of sweat samples taken from both forearms of the pateint was an average of 88.7 mM/L (normal value <40 mM/L). After a comprehensive search for mutations in the CFTR gene, the patient was found to carry the non-synonymous L441P mutation in one allele. Molecular physiologic analysis of the L441P mutation of CFTR revealed that the L441P mutation completely abolished the CFTR Cl- channel activity by disrupting proper protein folding and membrane trafficking of CFTR protein. These results confirmed the pathogenicity of the L441P mutation of CFTR circulating in the Korean population. The possibility of CF should be suspected in patients with chronic bronchiectasis, although the frequency of CF is relatively rare in East Asia.

Keyword

Bronchiectasis; Cl- channel; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Korea

MeSH Terms

Amino Acid Substitution
Base Sequence
Cell Line
Child, Preschool
Cystic Fibrosis/diagnosis/*genetics
Cystic Fibrosis Transmembrane Conductance Regulator/*genetics/metabolism
Female
Humans
Lung/radiography
*Mutation
Patch-Clamp Techniques
Republic of Korea
Tomography, X-Ray Computed
Cystic Fibrosis Transmembrane Conductance Regulator