Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a case of microbial keratitis in a patient with lamellar ichthyosis. An 11-year-old boy, a known case of lamellar ichthyosis, presented with microbial keratitis. Microbiological evaluation of corneal scraping revealed a mixed infection caused by gram-negative bacilli and gram-positive cocci. He was treated with topical ciprofloxacin and fortified cefazolin eyedrops. Microbial keratitis in patients with lamellar ichthyosis has a poor prognosis.
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PMID:Microbial keratitis in a case of lamellar ichthyosis. 1782 96

Keratitis-Ichthyosis-Deafness (KID) syndrome (OMIM 148210) is a congenital ectodermal defect. KID consists of an atypical ichthyosiform erythroderma associated with congenital sensorineural deafness. A rare form of the KID syndrome is a fatal course in the first year of life due to severe skin lesion infections and septicaemia. KID appears to be genetically heterogeneous and may be caused by mutations in connexin 26 or connexin 30 genes. GJB2 mutations in the connexin 26 gene are the main cause of the disease. Most of the cases caused by GJB2 mutations are sporadic, but dominant transmission has also been described. To date, the rare lethal form of the disease has been only observed in two Caucasian sporadic patients with the GJB2 mutation, with the p.Gly45Glu (G45E) arising de novo. We have reported an African family with dizygotic twins suffering from a lethal form of KID. The dizygosity of the twins was confirmed by microsatellite markers. The two patients were heterozygous for the G45E mutation of GJB2, whereas the mutation was not detected in the two parents. The unusual transmission of the disease observed in this family could be explained by the occurrence of a somatic or more probably a germinal mosaic in one of the parents.
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PMID:A familial case of Keratitis-Ichthyosis-Deafness (KID) syndrome with the GJB2 mutation G45E. 1802 54

KID syndrome is a rare congenital disorder characterized by keratitis, ichthyosis, and deafness. We have described a 4-year-old girl who is treated with bland emollients and topical keratolytics such as urea and surprisingly observed marked improvement in skin hyperkeratosis and palmoplantar keratoderma. We think that along with urgent ophthalmologic and otolaryngologic measures, simple topical therapies may improve skin condition in KID syndrome precluding the possible hazards of systemic retinoid therapy.
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PMID:KID syndrome. 1831 8

Keratitis ichthyosis deafness syndrome is a rare congenital ectodermal disorder. It appears to be genetically heterogeneous and may be caused by mutations in the connexin 26 (Cx26) gene (GJB2) or in the connexin 30 gene. It is characterized by the association of ichthyosis-like skin lesions, hearing loss, and vascularizing keratitis. We report the clinical and molecular findings in a 5-year-old girl with keratitis ichthyosis deafness syndrome. DNA sequencing in our patient revealed a p.Ser17Phe mutation in GJB2. Besides the typical clinical features of keratitis ichthyosis deafness syndrome, a peculiar intriguing finding not previously described in the literature in this condition was that polarizing light microscopy of the scalp hair in our patient revealed striking bright and dark bands as seen in trichothiodystrophy. Amino acid analysis of the hair sample also disclosed a reduced cysteine index. We emphasize that it would be of great benefit to examine hair shafts in other patients with keratitis ichthyosis deafness syndrome for trichothiodystrophy-like abnormalities.
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PMID:Trichothiodystrophy-like hair abnormalities in a child with keratitis ichthyosis deafness syndrome. 1878 90

The Keratitis-Ichthyosis-Deafness syndrome (KIDS) is an autosomal dominant ectodermal dysplasia characterized by ocular, skin, and ear anomalies, including keratitis, palmoplantar keratoderma, and congenital hearing loss. Most cases are due to mutations in the GJB2 gene encoding connexin 26. The Dandy-Walker malformation (DWM) is a developmental anomaly of the midline of the cerebellum with complete or partial agenesis of the vermis and cystic dilatation of the fourth ventricle. The association of KID syndrome with DWM has been reported a few times, but thought to be coincidental. We report 4 additional patients with KIDS and DWM, supporting the possibility that this is an association and not a coincidental finding. This also suggests that the GJB2 gene may have a role in other cases with DWM of, as yet, unknown etiology.
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PMID:Dandy-Walker malformation in patients with KID syndrome associated with a heterozygote mutation (p.Asp50Asn) in the GJB2 gene encoding connexin 26. 1979 13

Gap junctions allow the exchange of ions and small molecules between adjacent cells through intercellular channels formed by connexin proteins, which can also form functional hemichannels in nonjunctional membranes. Mutations in connexin genes cause a variety of human diseases. For example, mutations in GJB2, the gene encoding connexin-26 (Cx26), are not only a major cause of nonsyndromic deafness, but also cause syndromic deafness associated with skin disorders such as palmoplantar keratoderma, keratitis-ichthyosis deafness syndrome, Vohwinkel syndrome, hystrix-ichthyosis deafness syndrome and Bart-Pumphrey syndrome. The most common mutation in the Cx26 gene linked to nonsyndromic deafness is 35DeltaG, a frameshift mutation leading to an early stop codon. The large number of deaf individuals homozygous for 35DeltaG do not develop skin disease. Similarly, there is abundant experimental evidence to suggest that other Cx26 loss-of-function mutations cause deafness, but not skin disease. By contrast, Cx26 mutations that cause both skin diseases and deafness are all single amino acid changes. Since nonsyndromic deafness is predominantly a loss-of-function disorder, it follows that the syndromic mutants must show an alteration, or gain, of function to cause skin disease. Here, we summarise the functional consequences and clinical phenotypes resulting from Cx26 mutations that cause deafness and skin disease.
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PMID:Connexin-26 mutations in deafness and skin disease. 1993

Keratitis-ichthyosis-deafness (KID) syndrome is an autosomal dominant congenital ectodermal defect characterized by the association of skin lesions, hearing loss and keratitis. Most of the cases appear to be sporadic. KID syndrome is mostly related to mutations of GJB2 gene encoding connexin-26. Recently, a lethal form of the disease during the first year of life has been reported in two unrelated Caucasian patients. This rare lethal form is caused by the G45E mutation of GJB2 gene. We here report the first pre-natal molecular genetic diagnosis of the lethal form of KID syndrome relating to a G45E mutation. In the same family, the occurrence of this condition in three other siblings born to African non-consanguineous healthy parents lead to perform pre-natal diagnosis for this last pregnancy. Molecular analysis confirms the diagnosis of the lethal form of KID for the fetus. These results establish the role of germline mosaicism in KID syndrome and warrant careful genetic counseling. Furthermore, analysis of our cases and the literature allowed us to define a characteristic severe neonatal phenotype including facial dysmorphy, severe cornification with massive focal hyperkeratosis of the skin with erythroderma, dystrophic nails, complete atrichia and absence of foreskin.
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PMID:Germline mosaicism in keratitis-ichthyosis-deafness syndrome: pre-natal diagnosis in a familial lethal form. 2041 16

Mutations in GJB2, which encodes Cx26, are one of the most common causes of inherited deafness in humans. More than 100 mutations have been identified scattered throughout the Cx26 protein, most of which cause nonsyndromic sensorineural deafness. In a subset of mutations, deafness is accompanied by hyperkeratotic skin disorders, which are typically severe and sometimes fatal. Many of these syndromic deafness mutations localize to the amino-terminal and first extracellular loop (E1) domains. Here, we examined two such mutations, A40V and G45E, which are positioned near the TM1/E1 boundary and are associated with keratitis ichthyosis deafness (KID) syndrome. Both of these mutants have been reported to form hemichannels that open aberrantly, leading to "leaky" cell membranes. Here, we quantified the Ca(2+) sensitivities and examined the biophysical properties of these mutants at macroscopic and single-channel levels. We find that A40V hemichannels show significantly impaired regulation by extracellular Ca(2+), increasing the likelihood of aberrant hemichannel opening as previously suggested. However, G45E hemichannels show only modest impairment in regulation by Ca(2+) and instead exhibit a substantial increase in permeability to Ca(2+). Using cysteine substitution and examination of accessibility to thiol-modifying reagents, we demonstrate that G45, but not A40, is a pore-lining residue. Both mutants function as cell-cell channels. The data suggest that G45E and A40V are hemichannel gain-of-function mutants that produce similar phenotypes, but by different underlying mechanisms. A40V produces leaky hemichannels, whereas G45E provides a route for excessive entry of Ca(2+). These aberrant properties, alone or in combination, can severely compromise cell integrity and lead to increased cell death.
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PMID:Differentially altered Ca2+ regulation and Ca2+ permeability in Cx26 hemichannels formed by the A40V and G45E mutations that cause keratitis ichthyosis deafness syndrome. 2058 91

Keratitis, ichthyosis, deafness (KID) syndrome is a genetically determined disorder. The present case is having marked photophobia, bilateral corneal ulceration with vascularisation, neurosensory deafness and skin changes.
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PMID:Keratitis, ichthyosis and deafness (KID) syndrome. 2095 2

Connexin (Cx) proteins form intercellular gap junction channels by first assembling into single membrane hemichannels that then dock to connect the cytoplasm of two adjacent cells. Gap junctions are highly specialized structures that allow the direct passage of small molecules between cells to maintain tissue homeostasis. Functional activity of nonjunctional hemichannels has now been shown in several experimental systems. Hemichannels may constitute an important diffusional exchange pathway with the extracellular space, but the extent of their normal physiological role is currently unknown. Aberrant hemichannel activity has been linked to mutations of connexin proteins involved in genetic diseases. Here, we review a proposed role for hemichannels in the pathogenesis of Keratitis-Ichthyosis-Deafness (KID) syndrome associated with connexin26 (Cx26) mutations. Continued functional evaluation of mutated hemichannels linked to human hereditary disorders may provide additional insights into the mechanisms governing their regulation in normal physiology and dysregulation in disease. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.
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PMID:Pathological hemichannels associated with human Cx26 mutations causing Keratitis-Ichthyosis-Deafness syndrome. 2193 63


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