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Two cases of misinterpretation of molecular results in incontinentia pigmenti, and a PCR‐based method to discriminate NEMO/IKKγ dene deletion
Author(s) -
Bardaro Tiziana,
Falco Geppino,
Sparago Angela,
Mercadante Vincenzo,
Gean Molins Esther,
Tarantino Enrico,
Valeria Ursini Matilde,
D'Urso Michele
Publication year - 2003
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.10150
Subject(s) - incontinentia pigmenti , biology , pseudogene , genetics , exon , gene , hum , microbiology and biotechnology , genome , art , performance art , art history
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‐IKKγ) gene, which encodes a regulatory component of the IkB kinase complex, required to activate the NF‐kB pathway. In IP, mutations in NEMO lead to the complete loss of NF‐kB activation creating a susceptibility to cellular apoptosis in response to TNF‐α. 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, Δ 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 Δ 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.