DOES EVERYONE HAVE THE SAME MUTATION?
One characteristic of IP is the
variability of the severity and of the symptoms of the
disorder. Prior to the identification of the NEMO gene
defect, researchers expected this variability to be due to
different mutations present in different families. We now
know that about 85% of families have the same NEMO
mutation. Some variation in the disease is explained by
different (milder) mutations, however this is not the whole
explanation. With the identification of the gene, it has
become possible to begin to understand the reasons for such
variability in the disease, and it appears likely that the
variability is related to the pattern of inactivation of
the X chromosome in each individual patient.
The "Common" Mutation
The most common mutation in the NEMO gene that results in IP is a deletion of the majority of the gene that results from recombination between two repeated sequences in the gene. While this mutation is common to many patients, it happens spontaneously in families. Unlike other common mutations in other genetic diseases (such as Cystic Fibrosis) the IP mutation is not inherited from an ancestral mutation common to most families. Instead, it happens spontaneously in one member of the family, who then can pass it on to offspring.