Title
A novel DFNB1 deletion allele supports the existence of a distant **cis**-regulatory region that controls **GJB2** and **GJB6** expression A novel DFNB1 deletion allele supports the existence of a distant **cis**-regulatory region that controls **GJB2** and **GJB6** expression
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Publication type
article
Publication
Copenhagen ,
Subject
Human medicine
Source (journal)
Clinical genetics. - Copenhagen
Volume/pages
78(2010) :3 , p. 267-274
ISSN
0009-9163
ISI
000280629500007
Carrier
E
Target language
Dutch (dut)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Eleven affected members of a large GermanAmerican family segregating recessively inherited, congenital, non-syndromic sensorineural hearing loss (SNHL) were found to be homozygous for the common 35delG mutation of GJB2, the gene encoding the gap junction protein Connexin 26. Surprisingly, four additional family members with bilateral profound SNHL carried only a single 35delG mutation. Previously, we demonstrated reduced expression of both GJB2 and GJB6 mRNA from the allele carried in trans with that bearing the 35delG mutation in these four persons. Using array comparative genome hybridization (array CGH), we have now identified on this allele a deletion of 131.4 kb whose proximal breakpoint lies more than 100 kb upstream of the transcriptional start sites of GJB2 and GJB6. This deletion, del(chr13:19,837,34419,968,698), segregates as a completely penetrant DFNB1 allele in this family. It is not present in 528 persons with SNHL and monoallelic mutation of GJB2 or GJB6, and we have not identified any other candidate pathogenic copy number variation by arrayCGH in a subset of 10 such persons. Characterization of distant GJB2/GJB6 cis-regulatory regions evidenced by this allele may be required to find the 'missing' DFNB1 mutations that are believed to exist.
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