Fatal Septicemia in an Infant with Keratitis, Ichthyosis, and Deafness (KID) Syndrome

Gilliam, Amy E.; Williams, Mary L.

doi:10.1046/j.1525-1470.2002.00075.x

Cited by 53 publications

(46 citation statements)

References 41 publications

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“…Here, we report the functional characteristics of a Cx26 mutation (G45E) that was observed in two previously described infants with a rare fatal form of KIDS. The children harboring the G45E mutation in GJB2 had congenital deafness, hyper-keratosis of the skin, and recurrent severe skin infections, which eventually lead to septicemia and death within the first year of life (14,17,21). Using an in vitro expression assay, we show that Cx26-G45E hemichannels display a significant increase in membrane current flow that results in cell death.…”

mentioning

confidence: 94%

Aberrant hemichannel properties of Cx26 mutations causing skin disease and deafness

Gerido

DeRosa²,

Richard³

et al. 2007

American Journal of Physiology-Cell Physiology

122

157

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Mutations in the human GJB2 gene, which encodes connexin26 (Cx26), underlie various forms of hereditary deafness and skin disease. While it has proven difficult to discern the exact pathological mechanisms that cause these disorders, studies have shown that the loss or abnormal function of Cx26 protein has a profound effect on tissue homeostasis. Here, we used the Xenopus oocyte expression system to examine the functional characteristics of a Cx26 mutation (G45E) that results in keratitis-ichthyosis-deafness syndrome (KIDS) with a fatal outcome. Our data showed that oocytes were able to express both wild-type Cx26 and its G45E variant, each of which formed hemichannels and gap junction channels. However, Cx26-G45E hemichannels displayed significantly greater whole cell currents than wild-type Cx26, leading to cell lysis and death. This severe phenotype could be rescued in the presence of elevated Ca2+levels in the extracellular milieu. Cx26-G45E could also form intercellular channels with a similar efficiency as wild-type Cx26, however, with increased voltage sensitive gating. We also compared Cx26-G45E with a previously described Cx26 mutant, A40V, which has an overlapping human phenotype. We found that both dominant Cx26 mutants elicited similar functional consequences and that cells coexpressing mutant and wild-type connexins predominantly displayed mutant-like behavior. These data suggest that mutant hemichannels may act on cellular homeostasis in a manner that can be detrimental to the tissues in which they are expressed.

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mentioning

confidence: 94%

Aberrant hemichannel properties of Cx26 mutations causing skin disease and deafness

Gerido

DeRosa²,

Richard³

et al. 2007

American Journal of Physiology-Cell Physiology

122

157

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“…4 Sufferers from KID syndrome are more susceptible to bacterial and fungal infections of the skin and mucous membranes, mainly candida, which may be due to an intrinsic immunodeficiency, with death sometimes occurring in the first years of life. [5][6][7] A less frequent complication, but which can considerably decrease life expectancy of patients is squamous cell carcinoma, which occurs in 29% of cases. [4][5][6][7][8][9] A high probablility of extracutaneous involvement exists in KID syndrome.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7] A less frequent complication, but which can considerably decrease life expectancy of patients is squamous cell carcinoma, which occurs in 29% of cases. [4][5][6][7][8][9] A high probablility of extracutaneous involvement exists in KID syndrome. One manifestation is sensorineural deafness, generally with severe, bilateral and progressive evolution due to cochlear saccular dysplasia.…”

Section: Discussionmentioning

confidence: 99%

Você conhece esta síndrome?

Enei

Cassettari²,

Córdova³

et al. 2011

An. Bras. Dermatol.

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A síndrome de KID é uma displasia ectodérmica congênita rara que afeta a pele, o epitélio da córnea e o ouvido interno. Clinicamente, observam-se placas de eritroqueratodermia na face e pregas, geralmente presentes desde o nascimento, a surdez neurossensorial severa e bilateral, e a vascularização córnea associado à queratite de evolução progressiva à qual surge após as alterações cutâneas e auditivas na puberdade. Face ao quadro surdez, às infecções cutâneas, ao risco de cegueira e à degeneração maligna, o diagnóstico precoce da síndrome é fundamental, bem como o seguimento clínico periódico e o aconselhamento genético

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“…Deve-se atentar para a maior suscetibilidade a infecções e risco aumentado de desenvolvimento de tumores malignos, particularmente carcinoma de células escamosas (2)(3)(4)8) . A lubrificação intensa da superfície ocular vai reduzir as complicações.…”

Section: Discussionunclassified

“…Posteriormente, em 1981, estas alterações foram reconhecidas como uma displasia ectodérmica congênita rara, a síndrome KID -ceratite (K), ictiose (I) e surdez neurossensorial (D) (1) . Outros achados incluem alopécia, distrofia de unhas, anormalidades dentárias, maior risco para desenvolvimento de carcinoma de células escamosas e maior suscetibilidade para infecções bacterianas e fúngicas (2)(3)(4) . A maioria dos casos de síndrome KID é esporádica.…”

Section: Introductionunclassified