Familial recurrence of incontinentia pigmenti due to de novo pathogenic variants in the IKBKG gene.
IKBKG
de novo pathogenic variant
dominant X‐linked disorders
genetic diagnosis
incontinentia pigmenti
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
27 Mar 2024
27 Mar 2024
Historique:
revised:
30
01
2024
received:
14
11
2023
accepted:
02
03
2024
medline:
27
3
2024
pubmed:
27
3
2024
entrez:
27
3
2024
Statut:
aheadofprint
Résumé
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.
Identifiants
pubmed: 38536952
doi: 10.1002/ajmg.a.63591
doi:
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 Wiley Periodicals LLC.
Références
Aradhya, S., Woffendin, H., Jakins, T., Bardaro, T., Esposito, T., Smahi, A., Shaw, C., Levy, M., Munnich, A., D'Urso, M., Lewis, R. A., Kenwrick, S., & Nelson, D. L. (2001). A recurrent deletion in the ubiquitously expressed NEMO (IKK‐gamma) gene accounts for the vast majority of incontinentia pigmenti mutations. Human Molecular Genetics, 10(19), 2171–2179.
Fusco, F., Conte, M. I., Diociaiuti, A., Bigoni, S., Branda, M. F., Ferlini, A., El Hachem, M., & Ursini, M. V. (2017). Unusual father‐to‐daughter transmission of incontinentia pigmenti due to mosaicism in IP males. Pediatrics, 140(3), e20162950.
Fusco, F., Paciolla, M., Napolitano, F., Pescatore, A., D'Addario, I., Bal, E., Lioi, M. B., Smahi, A., Miano, M. G., & Ursini, M. V. (2012). Genomic architecture at the incontinentia pigmenti locus favours de novo pathological alleles through different mechanisms. Human Molecular Genetics, 21(6), 1260–1271.
Greene‐Roethke, C. (2017). Incontinentia pigmenti: A summary review of this rare ectodermal dysplasia with neurologic manifestations, including treatment protocols. Journal of Pediatric Health Care: Official Publication of National Association of Pediatric Nurse Associates & Practitioners, 31(6), e45–e52.
Kawai, M., Sugimoto, A., Ishihara, Y., Kato, T., & Kurahashi, H. (2022). Incontinentia pigmenti inherited from a father with a low level atypical IKBKG deletion mosaicism: A case report. BMC Pediatrics, 22(1), 378.
Parrish, J. E., Scheuerle, A. E., Lewis, R. A., Levy, M. L., & Nelson, D. L. (1996). Selection against mutant alleles in blood leukocytes is a consistent feature in incontinentia pigmenti type 2. Human Molecular Genetics, 5(11), 1777–1783.
Scheuerle, A. E., & Ursini, M. V. (1999). Incontinentia pigmenti. In M. P. Adam (Eds.) GeneReviews®. University of Washington.
Steffann, J., Raclin, V., Smahi, A., Woffendin, H., Munnich, A., Kenwrick, S. J., Grebille, A. G., Benachi, A., Dumez, Y., Bonnefont, J. P., & Hadj‐Rabia, S. (2004). A novel PCR approach for prenatal detection of the common NEMO rearrangement in incontinentia pigmenti. Prenatal Diagnosis, 24(5), 384–388.