IKBKG/NEMO

Molecular characteristics

IP has an X-linked inheritance although many affected individuals have IP as a result of a de novo pathogenic variant of the IKBKG/NEMO gene.
Molecular identification of the IKBKG/NEMO mutation is complicated by the presence of the IKBKG pseudogene. Therefore, the genetic diagnosis is performed following the three steps herein described:

  1. The search for the frequent 11.7 IKBKG/NEMO deletion, that is present in around 65% of IP patients is performed using PCR with standard method avoiding the identification of non-pathogenic variants in the pseudogene.
  2. The search for small intragenic deletions/insertions and missense, nonsense and splice site variants (8.6 % of IP patients) is performed using exon specific/gene specific PCR
  3. Gene-targeted deletion/duplication analysis (4% of IP patients) is performed using QPCR of IKBKG/NEMO locus to reveal non recurrent pathogenic deletion/insertion due to aberrant recombination.