Unusual father-to-daughter transmission of incontinentia pigmenti due to mosaicism in IP males

Francesca Fusco, Matilde Immacolata Conte, Andrea Diociauti, Stefania Bigoni, Maria Francesca Branda, Alessandra Ferlini, Maya El Hachem, Matilde Valeria Ursini

Research output: Contribution to journalArticlepeer-review

Abstract

Incontinentia pigmenti (IP; Online Mendelian Inheritance in Man catalog #308300) is an X-linked dominant ectodermal disorder caused by mutations of the inhibitor of κ polypeptide gene enchancer in B cells, kinase γ (IKBKG)/ nuclear factor κB, essential modulator (NEMO) gene. Hemizygous IKBKG/ NEMO loss-of-function (LoF) mutations are lethal in males, thus patients are female, and the disease is always transmitted from an IP-affected mother to her daughter. We present 2 families with father-to-daughter transmission of IP and provide for the first time molecular evidence that the combination of somatic and germ-line mosaicism for IKBKG/NEMO loss of function mutations in IP males resulted in the transmission of the disease to a female child. We searched for the IKBKG/NEMO mutant allele in blood, urine, skin, and sperm DNA and found that the 2 fathers were somatic and germ-line mosaics for the p.Gln132×mutation or the exon 4-10 deletion of IKBKG/ NEMO, respectively. The highest level of IKBKG/NEMO mutant cells was detected in the sperm, which might explain the recurrence of the disease. We therefore recommend careful clinical evaluation in IP male cases and the genetic investigation in sperm DNA to ensure correct genetic counseling and prevent the risk of paternal transmission of IP.

Original languageEnglish
Article numbere20162950
JournalPediatrics
Volume140
Issue number3
DOIs
Publication statusPublished - Sep 1 2017

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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