Last update: 05/06/2006
Background to disease
OMIM number: 220290
Gene OMIM number: 121011 (GJB2), 604418 (GJB6)
The GJB2 gene encodes connexin 26 (Cx26), a member of a family of gap junction proteins involved in cellular communication. Connexin 26 mutations may account for 10-30% of sporadic non-syndromic deafness. 35delG is the most common GJB2 mutation described so far (the deletion of one G within a stretch of six Gs at positions 30 to 35) and is found in the majority of families linked to locus DFNB1.
Over 80 additional mutations have so far been reported on The Connexin-deafness homepage (http://www.crg.es/deafness). The pathogenicity of some missense mutations has yet to be determined. Mutations in connexin 26 have also been reported in dominant (DFNA3) non-syndromic sensorineural hearing loss and in syndromic hearing loss.
Most of the mutations in GJB2 have been described in only one or a few individuals. 167delT has been found to be common in patients of Ashkenazi Jewish origin and 235delC has been found to be common amongst the Japanese and Chinese populations.
A large (342Kb) deletion involving connexin 30 (Cx30, GJB6), a gene in very close proximity to Cx26 has been found to cause deafness in the homozygous state and as a double heterozygote with Cx26 point mutations in trans.
Mitochondrial deafness
OMIM numbers 580000, 561000.0001
Sensorineural hearing loss is a frequent presentation of mitochondrial disease. Testing for the aminoglycoside induced 1555A>G mutation in families with maternally inherited deafness can be offered as appropriate.
Laboratory Analysis
Contact scientist: Jayne Rowland, David Cockburn
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Test |
Target reporting time (working days) |
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1. |
Direct sequencing of Cx26 exon 2 PCR of junction fragment of Cx30 deletion
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40 |
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2. |
RFLP for 1555A>G mutation (Mitochondrial) |
10 |