Big deletions or insertions affecting connexin genes causing deafness

Lerer et al, 2001 described the presence of a deletion of at least 140 Kb located upstream to the GJB2 gene and affecting the first exon of GJB6. This mutation is found in 7 patients from 4 independent Ashkenazi Jewish families, in trans with a mutation in the GJB2 gene, and it was not identified in 100 control subjects of the same origin.. The authors suggest that the deletion is a recessive mutation causing hearing loss in individuals that are double heterozygous for the deletion and a mutation in the GJB2 gene, either due to a digenic mode of inheritance or because the deletion abolishes control elements that are important in the expression of GJB2.

Pallares-Ruiz et al. 2002 have also described a deletion located 5" of the GJB6 gene, which probably is the same mutation, identified in several patients with French or Spanish origins, either in the homozygous state (one case) or in trans with a mutation in the GJB2 gene. The cloning of this mutation showed that it is the same one as described by del Castillo et al. 2002 (see below).

del Castillo et al, 2002 have identified and completely characterized a deletion that expands 342 kb and affects GJB6 but not the GJB2 gene. They have identified the deletion in both the homozygous state and in heterozygosity with mutations in GJB2.
They have also developed a specific diagnostic test for this mutation, which is the second most frequent mutation
causing prelingual deafness in the Spanish population. The data reported strongly suggest that DFNB1 could be due to either monogenic or digenic mutations in GJB2 and GJB6. It remains to be seen if this deletion,del(GJB6-D13S1830), is the same as the two previously reported deletions affecting GJB2.