Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The transcription factor NF-kappaB regulates the expression of numerous genes controlling the immune and stress responses, inflammatory reaction, cell adhesion, and protection against apoptosis. Incontinentia pigmenti (IP) is the first genetic disorder to be ascribed to NF-kappaB dysfunction. IP is an X-linked dominant genodermatosis antenatally lethal in males. A complex rearrangement of the NEMO (NF-kappaB essential modulator) gene accounts for 85% of IP patients, and results in undetectable NEMO protein and absent NF-kappaB activation. On the other hand, hypohidrotic/anhidrotic ectodermal dysplasia (HED/EDA) has been ascribed to at least three genes also involved in NF-kappaB activation: ectodysplasin (EDA1), EDA-receptor (EDAR) and EDAR-associated death domain (EDARADD). During hair follicle morphogenesis, EDAR is activated by ectodysplasin, and uses EDARADD as an adapter to build a signal transducing complex that leads to NF-kappaB activation. Hence, several forms of HED/EDA also result from impaired activation of the NF-kappaB cascade. Finally, hypomorphic NEMO mutations have been found to cause anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID), whilst stop codon mutations cause a more severe phenotype associating EDA-ID with osteopetrosis and lymphoedema (OL-EDA-ID). The immunological and infectious features observed in patients result from impaired NF-kappaB signalling, including cellular response to LPS, IL-1beta, IL-18, TNF-alpha, Tlr2 and CD40 ligand. Consistently, mouse knockout models have shown the essential role of NF-kappaB in the immune, inflammatory and apoptotic responses. Unravelling the molecular bases of other forms of EDA not associated with mutations in NEMO will possibly implicate other components of the NF-kappaB signalling pathway.
 ...
PMID:The NF-kappaB signalling pathway in human diseases: from incontinentia pigmenti to ectodermal dysplasias and immune-deficiency syndromes. 1235 72

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-IKKgamma) 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-alpha. 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, DeltaNEMO, 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 DeltaNEMO 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.
 ...
PMID:Two cases of misinterpretation of molecular results in incontinentia pigmenti, and a PCR-based method to discriminate NEMO/IKKgamma dene deletion. 1249 27

Incontinentia Pigmenti is an X-linked dominant neurocutaneous disorder with central nervous system manifestations in 30% of cases, including seizures and mental retardation. Ischemic or hemorrhagic cerebrovascular accidents have been reported rarely in incontinentia pigmenti. Chart review and literature search was performed following identification of the index case. We describe a patient with incontinentia pigmenti who developed bilateral cerebrovascular accidents in the neonatal period, with resultant severe neurologic sequelae. This is the second reported case of bilateral cerebrovascular accidents in a patient with incontinentia pigmenti. This finding may be secondary to cerebrovascular anomalies, similar to those observed in the retina. Recognition of cerebrovascular accidents as a complication of incontinentia pigmenti will hopefully lead to earlier recognition and treatment.
 ...
PMID:Bilateral cerebrovascular accidents in incontinentia pigmenti. 1367 26

Incontinentia pigmenti is a rare X-linked dominant disease that affects the ectodermal tissues and is usually lethal in males. Two girls, 1 Malay and 1 Chinese, with incontinentia pigmenti of the Bloch-Sulzberger type had a whorled pattern of scarring alopecia. This phenomenon, hitherto unreported in association with this disorder, corresponded to the lines of Blaschko. The mother and maternal grandmother of the Malay girl also had whorled scarring alopecia. This phenomenon is permanent and can be used as a marker to ascertain affected adult women who may no longer have cutaneous manifestations. X chromosome inactivation in females during early embryogenesis results in a mosaic population of cells, which explains the linear and patchy cutaneous manifestations of incontinentia pigmenti.
 ...
PMID:Whorled scarring alopecia: a rare phenomenon in incontinentia pigmenti? 1457 83

Incontinentia pigmenti, or Block-Sulzberger Syndrome, is an X-linked dominant disorder with characteristic skin, hair, eye and tooth abnormalities. It is classically considered a male-lethal disorder with recurrent miscarriages of male foetuses. A few cases of surviving males with incontinentia pigmenti have been reported in the medical literature. This article reports the medical and dental findings of a boy diagnosed with incontinentia pigmenti.
 ...
PMID:Surviving male with incontinentia pigmenti: a case report. 1470 31

Incontinentia pigmenti is an uncommon, inherited disorder with predominantly ectodermal manifestations that is associated with skin (100%)), dental (90%), skeletal (40%), central nervous (40%), and ocular (35%) deformities. It is an X-linked dominant disease, usually lethal in males and occurring in female infants. The dental effects include delayed eruption, partial anodontia, microdontia, and cone or peg-shaped teeth. The dental, clinical, and radiological findings in a 16-year-old female are presented here. The patient had peg-shaped teeth and a unilateral maxillary transverse discrepancy associated with oligodontia in the maxillary and mandibular arches. Orthodontic treatment included rapid maxillary expansion and fixed orthodontic therapy for prosthetic purposes and elimination of the functional midline shift.
 ...
PMID:Orthodontic and orthopedic treatment of a patient with incontinentia pigmenti. 1471 44

Familial incontinentia pigmenti (IP) (OMIM #308300) is a rare genetic disorder which segregates in an X-linked dominant way. The female-to-male ratio ranges from 20 to 37 : 1. In affected females IP causes highly variable abnormalities of the skin, hair, nails, teeth, eyes, and central nervous system (CNS). Cardiovascular anomalies, cerebral infarction, and immune dysfunction are rare complications of IP. The pathogenesis of cerebral changes in IP remains elusive. We report the case of two IP-affected sisters who presented in each case with neonatal seizures on the fifth day of life. Via cranial magnetic resonance tomographic imaging (MRI) different types of lesions in both hemispheres were demonstrable in both patients. To date the pathogenetic mechanisms for the cerebral lesions are not fully understood. However, multiple microscopic infarcts could serve as a possible explanation. The clinical course and the neurological development of the older child are favorable and so far the younger sibling appears to be developing normally, which is uncommon for patients with early onset of neurological symptoms. Symptomatic seizures in IP are an important differential diagnosis in benign non-familial and familial neonatal seizures.
 ...
PMID:Neonatal seizures in two sisters with incontinentia pigmenti. 1512 15

Incontinentia pigmenti (IP) is an X-linked dominant disorder of ectodermal structures affecting the skin, hair, teeth, eyes, and central nervous system. The four classic cutaneous stages of the disorder are well known to pediatric dermatologists. However, ocular and neurologic sequelae represent the major morbidity in IP. The two patients reported here highlight some of the potential ocular manifestations of IP and emphasize the importance of early ophthalmologic assessment in this condition.
 ...
PMID:The importance of screening for sight-threatening retinopathy in incontinentia pigmenti. 1516 4

Incontinentia Pigmenti (IP) is an X-linked genodermatosis that is lethal for males and present in females with abnormal skin pigmentation and high variable clinical signs, including retinal detachment, anodontia, alopecia, nail dystrophy and nervous system defects. The NF-kappaB essential modulator (NEMO) gene, responsible for IP, encodes the regulatory subunit of the IkappaB kinase (IKK) complex required for nuclear factor kappaB (NF-kappaB) activation. We analyzed the NEMO gene in 122 IP patients and identified mutations in 83 (36 familiar and 47 sporadic cases). The recurrent NEMO exon 4-10 deletion that is the major cause of the disease was present in 73 females (59.8%). In addition 10 point alterations (8.2% of females) were identified: three frameshift, three nonsense, three missense and one in-frame deletion of a single amino acid. We measured the effects of these NEMO point-mutations on NF-kappaB signaling in nemo(-/-) deficient murine pre-B cells. A mutation in the N-terminal domain, required for IKK assembly, reduced but did not abolish NF-kappaB activation following lipopolysaccharide stimulation. Mutations that disrupt the C-terminal domain, required for the recruitment of upstream factors, showed lower or no NF-kappaB activation. A phenotype score based on clinical features of our IP patients was applied for summarizing disease severity. The score did not correlate with mutation type or domain affected indicating that other factors influence the severity of IP. Such a factor is likely to be X-inactivation. Indeed, 64% of our patients have extremely skewed X-inactivation pattern (>/=80 : 20). Overall IP pathogenesis thus depends on a combination of X-inactivation and protein domain that recruit upstream factors and activate NF-kappaB.
 ...
PMID:Molecular analysis of the genetic defect in a large cohort of IP patients and identification of novel NEMO mutations interfering with NF-kappaB activation. 1522 84

Incontinentia pigmenti is an uncommon X-linked dominant genodermatosis primarily affecting females. Its hallmark is a unique skin eruption that presents in infancy along the lines of Blaschko and evolves through four stages: inflammatory, verrucous, hyperpigmented, and atrophic. Other persistent findings of the disease include alopecia and dental anomalies. In a minority of cases, serious ophthalmologic and neurological alterations may occur. Mutations in the NF-kappaB essential modulator (NEMO) that lead to an inability to activate the NF-kappaB pathway produce IP. Less deleterious mutations in NF-kappaB essential modulator give rise to hypohidrotic ectodermal dysplasia with immune deficiency in affected males, a related but distinct phenotype. These recent discoveries provide insight into the crucial role of NF-kappaB function in regulating the developmental, inflammatory, immune, and anti-apoptotic responses of the skin and other organs.
 ...
PMID:Incontinentia pigmenti: a window to the role of NF-kappaB function. 1529 21


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>