Cochleosaccular Dysplasia Associated With a Connexin 26 Mutation in Keratitis–Ichthyosis–Deafness Syndrome

Abstract

Objective-The objective of this study was to characterize the temporal bone phenotype associated with a mutation of GJB2 (encoding connexin 26).Study Design-The authors conducted correlative clinical, molecular genetic, and postmortem histopatho-logic analysis.Methods-The study subject was a male infant with keratitis-ichthyosis-deafness (KID) syndrome. We performed a nucleotide sequence analysis of GJB2 and a histopathologic analysis of the temporal bones.Results-The subject was heterozygous for G45E, a previously reported KID syndrome mutation of GJB2. The primary inner ear abnormality was dysplasia of the cochlear and saccular neuroepithelium.Conclusions-GJB2 mutations can cause deafness in KID syndrome, and possibly in other GJB2 mutant phenotypes, by disrupting cochlear differentiation.

Timed conditional null of connexin26 in mice reveals temporary requirements of connexin26 in key cochlear developmental events before the onset of hearing

“…Many aspects of this hypothesis still need experimental examinations, especially by findings from human specimen. One piece of supporting evidence is the observation that a dominant Cx26 mutation cause cochleosaccular dysplasia in the temporal bone examined from a 6 month old child (Griffith et al, 2006), which is consistent with the idea that Cx26 mutations in human could affect the cochlear development.…”

Carrier frequency of GJB2 (connexin-26) mutations causing inherited deafness in the Korean population

“…The possible causes of this duplication may be a slipped mispairing or homologous unequal recombination ). The p.G45E mutation is a nonconservative substitution in the N-terminal portion of the first extracellular loop of Cx26, in which most reported Keratitis-Ichthyosis-Deafness (KID) mutations are located (Griffith et al 2006). This mutation has also been detected in Japanese individuals with non-syndromic recessive deafness (Abe et al 2000;Oguchi et al 2005).…”

Aberrant hemichannel properties of Cx26 mutations causing skin disease and deafness

“…While the rare fatal form of KIDS has been associated with Cx26-G45E in two unrelated Caucasian patients (14,17,21), it has also been linked to recessive nonsyndromic deafness in some Asian populations. In a large study of Japanese patients with nonsyndromic SNHL, G45E was detected in 16% of the GJB2 disease alleles (26).…”

“…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.…”