Document Type
Article
Publication Date
7-10-2025
Identifier
DOI: 10.1016/j.xhgg.2025.100468; PMCID: PMC12256307
Abstract
Incontinentia pigmenti (IP) is caused by loss-of-function variants in IKBKG, with molecular genetic diagnosis complicated by a pseudogene. We describe seven individuals from three families with IP but negative clinical genetic testing in whom long-read sequencing identified causal variants, including one family with the common exon 4-10 deletion not identified by conventional clinical genetic testing. Concurrent methylation analysis explained disease severity in one individual who died from neurologic complications, identified a mosaic variant in an individual with an atypical presentation, and confirmed skewed X chromosome inactivation in an XXY individual.
Journal Title
HGG Adv
Volume
6
Issue
3
First Page
100468
Last Page
100468
MeSH Keywords
Humans; Incontinentia Pigmenti; Female; Male; I-kappa B Kinase; Pedigree; High-Throughput Nucleotide Sequencing; Child, Preschool; Infant; DNA Methylation
PubMed ID
40515401
Keywords
IKBKG; incontinentia pigmenti; long-read sequencing; methylation; pseudogene; skewed X chromosome inactivation; structural variation
Recommended Citation
Wojcik MH, Clark RD, Elias AF, et al. Long-read sequencing is required for precision diagnosis of incontinentia pigmenti. HGG Adv. 2025;6(3):100468. doi:10.1016/j.xhgg.2025.100468
Comments
This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.
Publisher's Link: https://linkinghub.elsevier.com/retrieve/pii/S2666-2477(25)00071-5