Genotype often cannot predict phenotype, but if you would like to research specific gene mutations the Cystic Fibrosis Mutation Database is a good place to start. You can search it, or try directly to:<a target=new class=ftalternatingbarlinklarge href="http://www.genet.sickkids.on.ca/cftr/">Text</a>
Also, the mutations are classified I-V, here's a summary I found:
Class I mutations lead to defects in the synthesis of stable CFTR mRNA transcripts resulting in absence of the CFTR protein. About half of all mutations in CFTR (encompassing premature termination, exon skipping, aberrant mRNA splicing, and frameshifts) are thought to fall into this class and result in complete loss of CFTR protein/function.
Class II mutations, including F508, complete protein translation but produce an abnormal protein that fails to escape the endoplasmic reticulum. Little or no CFTR reaches the plasma membrane, and the absence of all surface CFTR results in a severe phenotype. It is being increasingly recognized that mutations in unrelated genes can create defective proteins, which fail to traffic properly through the cell. Classically, missense mutations creating an abnormal protein were thought to be relatively benign or less consequential than nonsense mutations (null) or large deletions. This is no longer strictly the case because examples from CF and other inherited disorders demonstrate that a synthesized protein that fails to mature along the normal biosynthetic pathway often becomes quite destructive (7).
Class III mutations disrupt activation and regulation of CFTR at the plasma membrane. Thus biosynthesis, trafficking, and processing are undisturbed, but the channel may be defective with respect to ATP binding and hydrolysis, or phosphorylation. Mutations, such as G551D, tend to be associated with a severe phenotype.
Class IV mutations affect chloride conductance or channel gating and thus result in reduced chloride current. As might be expected, mutations in this class, such as R117H or P574H, are thought to confer a milder phenotype.
Class V mutations reduce the level of normal CFTR protein by alterations in the promoter or by altering splicing. Currently it is thought that a reduction in mRNA to less than 10% of normal results in disease in CF. Examples of Class V mutations include 3849 + 10kb CT, A455E, and 5T.
You may have to ask your doctor to identify the classification of your specific gene mutations. It's all pretty complicated but I think as parents we should try to be well informed. Hope this helps in some way.
Maria (mother of three daughters, the youngest, Samantha w/cf)
