Two cases of misinterpretation of molecular results in incontinentia pigmenti, and a PCR-based method to discriminate NEMO/IKK³ dene deletion

• Published in: Human mutation Vol. 21; no. 1; p. 8
• Main Authors: Bardaro, Tiziana, Falco, Geppino, Sparago, Angela, Mercadante, Vincenzo, Esther Gean Molins, Tarantino, Enrico, Ursini, Matilde Valeria, D'Urso, Michele
• Format: Journal Article
• Language: English
• Published: Hoboken Hindawi Limited 01.01.2003
• ISSN: 1059-7794; 1098-1004

Familial incontinentia pigmenti (IP) is a rare X-linked dominant disorder that affects ectodermal tissues. Over 90% of IP carrier females have a recurrent genomic deletion of exons 4-10 of the NEMO (IKBKG-IKK³) gene, which encodes a regulatory component of the IkB kinase complex, required to activate the NF-kB pathway. In IP, mutations in NEMOlead to the complete loss of NF-kB activation creating a susceptibility to cellular apoptosis in response to TNF-±. This condition is lethal for males during embryogenesis while females, who are mosaic as a result of X-inactivation, can survive. Recently, a second nonfunctional copy of the gene, [Delta]NEMO, was identified, opposite in direction to NEMO in a 35.5-kb duplicated sequence tract. PCR-based detection of the NEMO deletion is diagnostic for IP disease. However, we present instances in which ex 4-10 [Delta]NEMO pseudogene deletion occurs in unaffected parents of two females with clinically characteristic IP. These were missed by the currently standard PCR-based method, but can be easily discriminated by a new PCR-based test reported here that permits unambiguous molecular diagnosis and proper familial genetic counseling for IP. Hum Mutat 21:8-11, 2002. © 2002 Wiley-Liss, Inc.