Topic
Incontinentia pigmenti
About: Incontinentia pigmenti is a research topic. Over the lifetime, 1013 publications have been published within this topic receiving 16954 citations. The topic is also known as: Incontinentia pigmenti (disorder) & Incontinentia pigmenti syndrome (disorder).
Papers published on a yearly basis
Papers
More filters
••
TL;DR: Most cases of familial incontinentia pigmenti are due to mutations of this locus and that a new genomic rearrangement accounts for 80% of new mutations, which means that NF-κB activation is defective in IP cells.
Abstract: Familial incontinentia pigmenti (IP; MIM 308310) is a genodermatosis that segregates as an X-linked dominant disorder and is usually lethal prenatally in males. In affected females it causes highly variable abnormalities of the skin, hair, nails, teeth, eyes and central nervous system. The prominent skin signs occur in four classic cutaneous stages: perinatal inflammatory vesicles, verrucous patches, a distinctive pattern of hyperpigmentation and dermal scarring. Cells expressing the mutated X chromosome are eliminated selectively around the time of birth, so females with IP exhibit extremely skewed X-inactivation. The reasons for cell death in females and in utero lethality in males are unknown. The locus for IP has been linked genetically to the factor VIII gene in Xq28 (ref. 3). The gene for NEMO (NF-kappaB essential modulator)/IKKgamma (IkappaB kinase-gamma) has been mapped to a position 200 kilobases proximal to the factor VIII locus. NEMO is required for the activation of the transcription factor NF-kappaB and is therefore central to many immune, inflammatory and apoptotic pathways. Here we show that most cases of IP are due to mutations of this locus and that a new genomic rearrangement accounts for 80% of new mutations. As a consequence, NF-kappaB activation is defective in IP cells.
623 citations
••
TL;DR: A new X-linked recessive immunodeficiency syndrome is defined, distinct from other types of HED and immunODeficiency syndromes, and the data provide further evidence that the development of ectodermal appendages is mediated through a tumor necrosis factor/tumor necrosis factors receptor-like signaling pathway, with the IKK signalsome complex playing a significant role.
Abstract: Hypohidrotic ectodermal dysplasia (HED), a congenital disorder of teeth, hair, and eccrine sweat glands, is usually inherited as an X-linked recessive trait, although rarer autosomal dominant and recessive forms exist. We have studied males from four families with HED and immunodeficiency (HED-ID), in which the disorder segregates as an X-linked recessive trait. Affected males manifest dysgammaglobulinemia and, despite therapy, have significant morbidity and mortality from recurrent infections. Recently, mutations in IKK-gamma (NEMO) have been shown to cause familial incontinentia pigmenti (IP). Unlike HED-ID, IP affects females and, with few exceptions, causes male prenatal lethality. IKK-gamma is required for the activation of the transcription factor known as “nuclear factor kappa B” and plays an important role in T and B cell function. We hypothesize that “milder” mutations at this locus may cause HED-ID. In all four families, sequence analysis reveals exon 10 mutations affecting the carboxy-terminal end of the IKK-gamma protein, a domain believed to connect the IKK signalsome complex to upstream activators. The findings define a new X-linked recessive immunodeficiency syndrome, distinct from other types of HED and immunodeficiency syndromes. The data provide further evidence that the development of ectodermal appendages is mediated through a tumor necrosis factor/tumor necrosis factor receptor–like signaling pathway, with the IKK signalsome complex playing a significant role.
464 citations
••
TL;DR: The results indicate that the mouse model for the human genetic disorder incontinentia pigmenti, together with the recent discovery that mutations in the human NEMO gene cause IP, is created.
413 citations
••
TL;DR: It is proposed that the IKK gamma/NEMO-deficient cells trigger an inflammatory reaction that eventually leads to their death, and this unique self-limiting disease, the first to be genetically linked to the Ikk signaling pathway, is dependent on X-chromosome inactivation.
391 citations
••
TL;DR: This work reviewed 464 references from the world literature and found 653 apparently valid reports of patients with incontinentia pigmenti, which is an uncommon genodermatosis that usually affects female infants.
Abstract: • Incontinentia pigmenti (Bloch-Sulzberger syndrome) is an uncommon genodermatosis that usually affects female infants. I reviewed 464 references from the world literature and found 653 apparently valid reports of patients with incontinentia pigmenti. Skin manifestations were found to be somewhat more common than previously reported, and systemic manifestations were found in 79.8% of the patients. (Arch Dermatol112:535-542, 1976)
353 citations