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Pivot Concepts:
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Target Concepts:
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Query: UMLS:C0036690 (
sepsis
)
59,461
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Keratitis-ichthyosis-deafness syndrome
is a well-characterized disease that has been related to mutations in the GJB6 gene. Clinical features such as erythrokeratoderma, palmoplantar keratoderma, alopecia, and progressive vascularizing keratitis, among others, are well known in this entity. In this report we describe a newborn female patient diagnosed with
keratitis-ichthyosis-deafness syndrome
with a lethal outcome due to
sepsis
. The patient harbored the mutation A88V that has been previously reported in lethal cases.
...
PMID:Lethal Keratitis, Ichthyosis, and Deafness Syndrome Due to the A88V Connexin 26 Mutation. 2740 1
We characterized a novel
GJB2
missense variant, c.133G>A, p.Gly45Arg, and compared it with the only other variant at the same amino acid position of the connexin 26 protein (Cx26) reported to date: c.134G>A, p.Gly45Glu. Whereas both variants are associated with hearing loss and are dominantly inherited, p.Gly45Glu has been implicated in the rare fatal
keratitis-ichthyosis-deafness (KID) syndrome
, which results in cutaneous infections and
septicemia
with premature demise in the first year of life. In contrast, p.Gly45Arg appears to be non-syndromic. Subcellular localization experiments in transiently co-transfected HeLa cells demonstrated that Cx26-WT (wild-type) and p.Gly45Arg form gap junctions, whereas Cx26-WT with p.Gly45Glu protein does not. The substitution of a nonpolar amino acid glycine in wildtype Cx26 at position 45 with a negatively charged glutamic acid (acidic) has previously been shown to interfere with Ca
2+
regulation of hemichannel gating and to inhibit the formation of gap junctions, resulting in cell death. The novel variant p.Gly45Arg, however, changes this glycine to a positively charged arginine (basic), resulting in the formation of dysfunctional gap junctions that selectively affect the permeation of negatively charged inositol 1,4,5-trisphosphate (IP
3
) and contribute to hearing loss. Cx26 p.Gly45Arg transfected cells, unlike cells transfected with p.Gly45Glu, thrived at physiologic Ca
2+
concentrations, suggesting that Ca
2+
regulation of hemichannel gating is unaffected in Cx26 p.Gly45Arg transfected cells. Thus, the two oppositely charged amino acids that replace the highly conserved uncharged glycine in p.Gly45Glu and p.Gly45Arg, respectively, produce strikingly different effects on the structure and function of the Cx26 protein.
...
PMID:Comparative functional characterization of novel non-syndromic
GJB2
gene variant p.Gly45Arg and lethal syndromic variant p.Gly45Glu. 2776 13
