Please note: While some information will still be current in a year, other information may already be out of date in three months time. If you are in any doubt, please feel free to ask.

Classes of genes

Question
What are the classes of CF gene mutations? Thank you
Answer
Thank you for your question. The various mutations can be grouped into 6 different classes based on their predicted or known impact on mechanisms of dysfunction for the CFTR protein. This classification provides an indication of a mutation’s severity and so provides a rationale for their phenotypic consequences.
Class 1 mutations lead to defective protein synthesis in the cell and so there is no CFTR protein at the apical membrane resulting in a severe CF phenotype. In class 2 mutations there is abnormal processing and trafficking of CFTR resulting in minimal, or indeed absent, functional CFTR protein at the apical membrane. The mutations in this class tend to confer a severe disease, but this varies considerably. Mutations in class 3 have defective regulation of CFTR, and so although there is a normal amount of CFTR at the apical membrane, it is not functionally normal. Mutations in class 3 tend to have a milder disease than class 2 mutations. A decreased conductance of a normal amount of CFTR is characteristic of class 4 mutations. CF subjects with class 4 mutations tend to have a mild CF phenotype. There is a reduced synthesis or trafficking of CFTR in class 5 mutations leading to a reduced amount of functional CFTR at the apical membrane. This also results in mild disease. Finally, CFTR in class 6 mutations has decreased stability. Class 6 mutations are associated with a severe CF presentation.[1]

Best wishes
Dr David Comer
Belfast

Reference List
1. Zielenski, J., Genotype and phenotype in cystic fibrosis. Respiration, 2000. 67(2): p. 117-33.
19.01.2012