Pediatric cholesteatoma and variants in the gene encoding connexin 26.
OBJECTIVE
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.


METHODS
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.
James
Adrian L
AL
Department of Otolaryngology, The Hospital for Sick Children, Ontario, Canada. adr.james@utoronto.ca
Chadha
Neil K
NK
Papsin
Blake C
BC
Stockley
Tracy L
TL
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002781:Cholesteatoma / Q000235:genetics*; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011446:Prospective Studies
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26