Iris Schrijver

Publication Details

  • The digenic hypothesis unraveled: The GJB6 del(GJB6-D13S1830) mutation causes allele-specific loss of GJB2 expression in cis BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS Rodriguez-Paris, J., Schrijver, I. 2009; 389 (2): 354-359


    Connexin 26 and connexin 30 are the major connexins expressed in the cochlea, where they are co-localized and form heteromeric gap junctions. Mutations in the GJB2 gene, which encodes connexin 26, are the most common cause of prelingual non-syndromic sensorineural hearing loss. The large del(GJB6-D13S1830) mutation which involves GJB6 (connexin 30), causes hearing loss in homozygous individuals, or when compound heterozygous with a GJB2 mutation. Until now, it remained unresolved whether this phenomenon results from digenic inheritance or because of lack of GJB2 mRNA expression. After RNA extraction from buccal epithelium, a tissue known to express connexin 26 as well as connexin 30, allele-specific expression of GJB2 was investigated by reverse-transcriptase PCR and restriction digestions in three unrelated individuals compound heterozygous for a GJB2 mutation and del(GJB6-D13S1830). Each proband carried a different sequence change in GJB2. The mutated GJB2 allele in trans with del(GJB6-D13S1830) was expressed in all three individuals whereas the GJB2 allele located in cis with the deletion was not expressed at all. Thus, mutations in these two genes do not cause hearing loss through a digenic mechanism of inheritance alone, as was postulated previously, but instead GJB2 expression is abolished through an effect in cis with the deletion. Our study provides unequivocal support for the hypothesis that del(GJB6-D13S1830) eliminates a putative cis-regulatory element located within the deleted region.

    View details for DOI 10.1016/j.bbrc.2009.08.152

    View details for Web of Science ID 000270764400028

    View details for PubMedID 19723508

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