Genetic of IP
IP is due to a mutation of the IKBKG/NEMO gene (Inhibitor of Kappa polypeptide gene enhancer in B-cells, Kinase Gamma/Nuclear Factor kappaB, Essential Modulator) located on X-chromosome in the Xq28 region.
83% of cases have a recurrent deletion (del4-10), removing exons 4–10 of the IKBKG/NEMO gene; the 2% have non-recurrent genomic deletions in the IP locus; the 9% have point mutations in the NEMO coding region; and the 6% lack any known NEMO mutation.
The IP inheritance is X-linked, and it is lethal in males. The patients are females and they have in heterozigous state the mutation in NEMO gene.
Most IKBKG/NEMO mutations are de novo, and the IP syndrome is typically a sporadic condition (>70% of cases).