The Impact of the IKBKG Gene on the Appearance of the Corpus Callosum Abnormalities in Incontinentia Pigmenti

Incontinentia pigmenti (IP) is a rare skin disease combined with anomalies of the teeth, eyes, and central nervous system (CNS). Mutations of the IKBKG gene are responsible for IP. Among the most frequent CNS abnormalities found in IP using magnetic resonance imaging (MRI) are corpus callosum (CC) abnormalities. The aim of the study was to determine the presence of CC abnormalities, their relationship with the IKBKG mutations, and the possible presence of mutations of other genes. A group of seven IP patients was examined. Analyses of the IKBKG gene and the X-chromosome inactivation pattern were performed, as well as MRI and whole exome sequencing (WES) with the focus on the genes relevant for neurodegeneration. WES analysis showed IKBKG mutation in all examined patients. A patient who had a mutation of a gene other than IKBKG was excluded from further study. Four of the seven patients had clinically diagnosed CNS anomalies; two out of four had MRI-diagnosed CC anomalies. The simultaneous presence of IKBKG mutation and CC abnormalities and the absence of other mutations indicate that IKBKG may be the cause of CC abnormalities and should be included in the list of genes responsible for CC abnormalities.

Automated summary

Incontinentia pigmenti (IP) is a rare skin disease accompanied by anomalies in teeth, eyes, and the central nervous system (CNS). Mutations in the IKBKG gene are responsible for IP. Magnetic resonance imaging (MRI) showed that corpus callosum (CC) abnormalities were the most common CNS abnormalities in IP. This study aimed to identify CC abnormalities, their relationship with IKBKG mutations, and the possible presence of mutations in other genes. A group of seven IP patients were examined, and genetic analyses, MRI, and whole exome sequencing (WES) were performed. WES analysis revealed IKBKG mutations in all patients. One patient with a mutation in a gene other than IKBKG was excluded from further study. Among the four patients with clinically diagnosed CNS anomalies, two had MRI-diagnosed CC abnormalities. The coexistence of IKBKG mutation and CC abnormalities, along with the absence of other mutations, suggests that IKBKG may be responsible for CC abnormalities.