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Familial recurrence of incontinentia pigmenti due to de novo pathogenic variants in the IKBKG gene.

Julie SteffannJudite De Oliveira SantosAnne-Laure ZelbinSmail Hadj RabiaFabienne Charbit-HenrionFlorence Petit
Published in: American journal of medical genetics. Part A (2024)
Incontinentia pigmenti (IP, Bloch-Sulzberger syndrome) is a multisystem disorder which associates specific skin lesions that evolves in four stages, and occasionally, central nervous system, eye, hair, and teeth involvement. Familial (35%) and sporadic (65%) cases are caused by pathogenic variants in the IKBKG gene. Here we report an unusual family, where, in two half-sisters affected by typical IP, molecular genetic analysis identified a likely pathogenic non-sense variant in the IKBKG gene of one of the sisters, the other being not a carrier. The strong clinical conviction motivated further molecular genetic investigations, which led to the characterization of a second variant in this unique family. X chromosome inactivation studies demonstrated the paternal origin of these two de novo variants. For genes with frequent de novo mutations, the coexistence of different pathogenic mutations in the same family is a possibility, and constitutes a challenge for genetic counseling.
Keyphrases
  • copy number
  • genome wide
  • dna methylation
  • genome wide identification
  • early onset
  • late onset
  • single molecule
  • gene expression
  • smoking cessation
  • human immunodeficiency virus
  • free survival