Successful cochlear implantation in a child with Keratosis, Icthiosis and Deafness (KID) Syndrome and Dandy-Walker malformation

Cushing, Sharon L.; MacDonald, Laurie; Propst, Evan J.; Sharma, Alok; Stockley, Tracy L.; Blaser, Susan; James, Adrian L.; Papsin, Blake C.

doi:10.1016/j.ijporl.2008.01.017

Cited by 21 publications

(15 citation statements)

References 24 publications

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“…In all of our in vitro assays, the magnitude of hemichannel current produced by Cx26-D50A was less than that of Cx26-A88V, particularly at negative membrane potentials. The disease progression in the Cx26-D50A patient was also less severe (6), particularly compared with the lethal outcome in the two reported cases of children with the Cx26-A88V mutation (15,20), suggesting that severity of KID syndrome may correlate with the relative increase in hemichannel activity caused by the respective mutation.…”

Section: Discussionmentioning

confidence: 75%

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The human Cx26-D50A and Cx26-A88V mutations causing keratitis-ichthyosis-deafness syndrome display increased hemichannel activity

Mhaske

Levit

et al. 2013

American Journal of Physiology-Cell Physiology

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Mutations in the human gene encoding connexin 26 (Cx26 or GJB2) cause either nonsyndromic deafness or syndromic deafness associated with skin diseases. That distinct clinical disorders can be caused by different mutations within the same gene suggests that different channel activities influence the ear and skin. Here we use three different expression systems to examine the functional characteristics of two Cx26 mutations causing either mild (Cx26-D50A) or lethal (Cx26-A88V) keratitis-ichthyosis-deafness (KID) syndrome. In either cRNA-injected Xenopus oocytes, transfected HeLa cells, or transfected primary human keratinocytes, we show that both Cx26-D50A and Cx26-A88V form active hemichannels that significantly increase membrane current flow compared with wild-type Cx26. This increased membrane current accelerated cell death in low extracellular calcium solutions and was not due to increased mutant protein expression. Elevated mutant hemichannel currents could be blocked by increased extracellular calcium concentration. These results show that these two mutations exhibit a shared gain of functional activity and support the hypothesis that increased hemichannel activity is a common feature of human Cx26 mutations responsible for KID syndrome.

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Section: Discussionmentioning

confidence: 75%

“…1 Cx26-D50A was identified in one child with profound deafness, corneal abnormalities, hyperkeratosis, and Dandy-Walker malformation (6). Cx26-A88V has been described in two pediatric patients with the lethal form of KID syndrome.…”

mentioning

confidence: 98%

The human Cx26-D50A and Cx26-A88V mutations causing keratitis-ichthyosis-deafness syndrome display increased hemichannel activity

Mhaske

Levit

et al. 2013

American Journal of Physiology-Cell Physiology

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“…Some types are associated with SNHL, such as Vohwinkel syndrome (palmoplantar keratoderma and SNHL), 4 Bart-Pumphrey syndrome (hyperkeratotic knuckles, leukonychia, and SNHL), 5 and KID syndrome (keratitis, ichthyosis, and deafness). 6 These skin conditions are due to dominant mutations at particular sites in the GJB2 gene instead of the recessive mutations more commonly found in nonsyndromic SNHL. A more subtle skin change is noted with the GJB2 mutation R143W.…”

Section: Introductionmentioning

confidence: 99%

Pediatric cholesteatoma and variants in the gene encoding connexin 26

et al. 2009

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Objectives/Hypothesis: Connexin 26 is a gap junction protein encoded by the GJB2 gene. It is expressed in cholesteatoma, and mutations cause proliferative skin disorders and sensorineural hearing loss (SNHL). Deletions of GJB6, which encodes connexin 30, cause SNHL in a digenic manner with a heterozygous GJB2 mutation. We hypothesize that GJB2 and GJB6 mutations might influence the development of cholesteatoma.Study Design: Prospective observational study to identify GJB mutations in pediatric cholesteatoma.Methods: Peripheral blood samples from 98 children with cholesteatoma were screened for mutations in the GJB2 gene by direct sequencing of the coding region (exon 2 and the intron/exon boundary). Deletions of the GJB6 gene were tested using multiple ligation probe amplification methods. GJB status was compared with other populations and patient age and extent of cholesteatoma at presentation.Results: Fourteen children had at least one GJB2 variant (14%). Of these, three had two variants. Two of the variants were neutral polymorphisms. One child with the GJB2 genotype 35delG/35delG also had SNHL. No correlation was found between GJB2 status and patient age or cholesteatoma severity at presentation. No GJB6 deletions were found.Conclusions: GJB2 gene variants are present in a minority of children with cholesteatoma, but may be more common than in normal populations. It is conceivable that alterations of connexin 26 expression could contribute to the multifactorial disease process in cholesteatoma by modifying the cell-to-cell communication that is important in proliferation and migration of keratinocytes.

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“…All three children achieved useful speech perception at least 9 months postoperatively and positive communication outcomes up to 6 years post-operatively. Cushing et al (2008) document a patient with an initial mild post-operative wound infection treated with topical and oral antibiotics but good audiological outcome at 3 years. One centre implanted a patient without any complication (Choung et al, 2008), and for the last patient no outcome data were published (Lenane et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Cochlear implantation in keratitis–ichthyosis–deafness syndrome – 10-year follow-up of two patients

Smyth

Sinnathuray

Hughes

et al. 2012

Cochlear Implants International

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Successful cochlear implantation in a child with Keratosis, Icthiosis and Deafness (KID) Syndrome and Dandy-Walker malformation

Cited by 21 publications

References 24 publications

The human Cx26-D50A and Cx26-A88V mutations causing keratitis-ichthyosis-deafness syndrome display increased hemichannel activity

The human Cx26-D50A and Cx26-A88V mutations causing keratitis-ichthyosis-deafness syndrome display increased hemichannel activity

Pediatric cholesteatoma and variants in the gene encoding connexin 26

Cochlear implantation in keratitis–ichthyosis–deafness syndrome – 10-year follow-up of two patients

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