Please note: While some information will still be current in a year, other information may already be out of date in three months time.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