GJB2 encodes the protein Connexin 26, one of the building blocks of gap jun
ctions. Each Connexin 26 molecule can oligomerize with five other connexins
to form a connexon; two connexons, in turn, can form a gap junction. Becau
se mutations in GJB2 are the most common cause of congenital severe-to-prof
ound autosomal recessive nonsyndromic hearing loss, the effect of the Conne
xin 26 allele variants on this dynamic 'construction' process and the funct
ion of any gap junctions that do form is particularly germane. One of the m
ore controversial allele variants, M34T, has been hypothesized to cause aut
osomal dominant nonsyndromic hearing loss. In this paper, we present clinic
al and genotypic data that refutes this hypothesis and suggests that the ef
fect of the M34T allele variant may be dependent on the mutations segregati
ng in the opposing allele.