A new mutation in exon 7 of NEMO gene: late skewed X-chromosome inactivation in an incontinentia pigmenti female patient with immunodeficiency.
Hum Genet
; 118(3-4): 458-65, 2005 Dec.
Article
em En
| MEDLINE
| ID: mdl-16228229
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 (NEMODelta4-10), although other mutations have been reported. Mutations of NEMO which do not abolish NF-kappaB 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-kappaB pathway in T cell homeostasis. The decreased NEMO protein amount and the impaired IkBalpha 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.
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Base de dados:
MEDLINE
Assunto principal:
Incontinência Pigmentar
/
Cromossomos Humanos X
/
Quinase I-kappa B
/
Doenças do Sistema Imunitário
Limite:
Female
/
Humans
/
Infant
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article