Misprocessing of the CFTR protein leads to mild cystic fibrosis phenotype
Cystic fibrosis (CF) is mainly caused by mutations that interfere with the biosynthetic folding of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. The aim of this study was to determine the mechanism of dysfunction of a disease‐causing mutation associated with variab...
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Veröffentlicht in: | Human mutation 2005-04, Vol.25 (4), p.360-371 |
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Sprache: | eng |
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Zusammenfassung: | Cystic fibrosis (CF) is mainly caused by mutations that interfere with the biosynthetic folding of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. The aim of this study was to determine the mechanism of dysfunction of a disease‐causing mutation associated with variable phenotypes. In order to attain these objectives, we studied the effect of the p.L206W mutation on CFTR protein production and function, and we examined the genotype–phenotype correlation of [p.L206W]+[p.F508del] patients. We showed that p.L206W is a processing (class II) mutation since the CFTR biosynthetic pathway was severely impaired, whereas single‐channel measurements indicated ion conductance similar to the wild‐type protein. These data raise the larger question of the phenotypic variability of class II mutants, including p.F508del. Since multiple potential partners could modify the processing of the CFTR protein during its course to the cell surface, environmental and other genetic factors might contribute to this variability. Hum Mutat 25:360–371, 2005. © 2005 Wiley‐Liss, Inc. |
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ISSN: | 1059-7794 1098-1004 |
DOI: | 10.1002/humu.20156 |