A new mutation in exon 7 of NEMO gene: late skewed X-chromosome inactivation in an incontinentia pigmenti female patient with immunodeficiency |
| |
Authors: | Natalia Martinez-Pomar Ivan Munoz-Saa Damian Heine-Suner Ana Martin Asma Smahi Nuria Matamoros |
| |
Affiliation: | (1) Immunology Service, Hospital Universitari Son Dureta, Andrea Doria, 55, 07014 Palma de Mallorca, Balearic Islands, Spain;(2) Genetic Service, Hospital Universitari Son Dureta, Palma de Mallorca, Balearic Islands, Spain;(3) Dermatology Service, Hospital Universitari Son Dureta, Palma de Mallorca, Balearic Islands, Spain;(4) Departement de Genetique et Unite de Recherches sur les Handicaps Genetiques de l’Enfant INSERM UR-393, Hospital Necker, Paris, France |
| |
Abstract: | Incontinentia pigmenti is an X-linked genodermatosis, lethal in males. Affected females survive because of X-chromosome dizygosity and negative selection of cells carrying the mutant X-chromosome, and for this reason the skewed X inactivation pattern is often used to confirm the diagnosis. The most frequent mutation is a deletion of part of the NEMO gene (NEMOΔ4–10), although other mutations have been reported. Mutations of NEMO which do not abolish NF-κB activity totally permit male survival, causing an allelic variant of IP called hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID). We present a non-classical IP female patient who also suffered transient immunodeficiency because of a late and progressive selection against peripheral blood cells carrying an active mutated X-chromosome. This finding suggests that in the absence of known mutation the X-inactivation studies used in genetic counselling can induce mistakes with some female patients. At the age of 3 years and 6 months, all immunodeficiency signs disappeared, and the X-chromosome inactivation pattern was completely skewed. The low T cell proliferation and CD40L expression corroborate the important role of NEMO/ NF-κB pathway in T cell homeostasis. The decreased NEMO protein amount and the impaired IkBα degradation suggest that this new mutation, NM_003639: c.1049dupA, causes RNA or protein instability. To our knowledge, this is the first time that selection against the mutated X-chromosome in X-linked disease has been documented in vivo. |
| |
Keywords: | |
本文献已被 PubMed SpringerLink 等数据库收录! |
|