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Allele-Specific Impairment of GJB2 Expression by GJB6 Deletion del(GJB6-D13S1854)
Mutations in the GJB2 gene, which encodes connexin 26, are a frequent cause of congenital non-syndromic sensorineural hearing loss. Two large deletions, del(GJB6-D13S1830) and del(GJB6-D13S1854), which truncate GJB6 (connexin 30), cause hearing loss in individuals homozygous, or compound heterozygou...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126855/ https://www.ncbi.nlm.nih.gov/pubmed/21738759 http://dx.doi.org/10.1371/journal.pone.0021665 |
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author | Rodriguez-Paris, Juan Tamayo, Marta L. Gelvez, Nancy Schrijver, Iris |
author_facet | Rodriguez-Paris, Juan Tamayo, Marta L. Gelvez, Nancy Schrijver, Iris |
author_sort | Rodriguez-Paris, Juan |
collection | PubMed |
description | Mutations in the GJB2 gene, which encodes connexin 26, are a frequent cause of congenital non-syndromic sensorineural hearing loss. Two large deletions, del(GJB6-D13S1830) and del(GJB6-D13S1854), which truncate GJB6 (connexin 30), cause hearing loss in individuals homozygous, or compound heterozygous for these deletions or one such deletion and a mutation in GJB2. Recently, we have demonstrated that the del(GJB6-D13S1830) deletion contributes to hearing loss due to an allele-specific lack of GJB2 mRNA expression and not as a result of digenic inheritance, as was postulated earlier. In the current study we investigated the smaller del(GJB6-D13S1854) deletion, which disrupts the expression of GJB2 at the transcriptional level in a manner similar to the more common del(GJB6-D13S1830) deletion. Interestingly, in the presence of this deletion, GJB2 expression remains minimally but reproducibly present. The relative allele-specific expression of GJB2 was assessed by reverse-transcriptase PCR and restriction digestions in three probands who were compound heterozygous for a GJB2 mutation and del(GJB6-D13S1854). Each individual carried a different sequence variant in GJB2. All three individuals expressed the mutated GJB2 allele in trans with del(GJB6-D13S1854), but expression of the GJB2 allele in cis with the deletion was almost absent. Our study clearly corroborates the hypothesis that the del(GJB6-D13S1854), similar to the larger and more common del(GJB6-D13S1830), removes (a) putative cis-regulatory element(s) upstream of GJB6 and narrows down the region of location. |
format | Online Article Text |
id | pubmed-3126855 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31268552011-07-07 Allele-Specific Impairment of GJB2 Expression by GJB6 Deletion del(GJB6-D13S1854) Rodriguez-Paris, Juan Tamayo, Marta L. Gelvez, Nancy Schrijver, Iris PLoS One Research Article Mutations in the GJB2 gene, which encodes connexin 26, are a frequent cause of congenital non-syndromic sensorineural hearing loss. Two large deletions, del(GJB6-D13S1830) and del(GJB6-D13S1854), which truncate GJB6 (connexin 30), cause hearing loss in individuals homozygous, or compound heterozygous for these deletions or one such deletion and a mutation in GJB2. Recently, we have demonstrated that the del(GJB6-D13S1830) deletion contributes to hearing loss due to an allele-specific lack of GJB2 mRNA expression and not as a result of digenic inheritance, as was postulated earlier. In the current study we investigated the smaller del(GJB6-D13S1854) deletion, which disrupts the expression of GJB2 at the transcriptional level in a manner similar to the more common del(GJB6-D13S1830) deletion. Interestingly, in the presence of this deletion, GJB2 expression remains minimally but reproducibly present. The relative allele-specific expression of GJB2 was assessed by reverse-transcriptase PCR and restriction digestions in three probands who were compound heterozygous for a GJB2 mutation and del(GJB6-D13S1854). Each individual carried a different sequence variant in GJB2. All three individuals expressed the mutated GJB2 allele in trans with del(GJB6-D13S1854), but expression of the GJB2 allele in cis with the deletion was almost absent. Our study clearly corroborates the hypothesis that the del(GJB6-D13S1854), similar to the larger and more common del(GJB6-D13S1830), removes (a) putative cis-regulatory element(s) upstream of GJB6 and narrows down the region of location. Public Library of Science 2011-06-29 /pmc/articles/PMC3126855/ /pubmed/21738759 http://dx.doi.org/10.1371/journal.pone.0021665 Text en Rodriguez-Paris et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Rodriguez-Paris, Juan Tamayo, Marta L. Gelvez, Nancy Schrijver, Iris Allele-Specific Impairment of GJB2 Expression by GJB6 Deletion del(GJB6-D13S1854) |
title | Allele-Specific Impairment of GJB2 Expression by GJB6 Deletion del(GJB6-D13S1854) |
title_full | Allele-Specific Impairment of GJB2 Expression by GJB6 Deletion del(GJB6-D13S1854) |
title_fullStr | Allele-Specific Impairment of GJB2 Expression by GJB6 Deletion del(GJB6-D13S1854) |
title_full_unstemmed | Allele-Specific Impairment of GJB2 Expression by GJB6 Deletion del(GJB6-D13S1854) |
title_short | Allele-Specific Impairment of GJB2 Expression by GJB6 Deletion del(GJB6-D13S1854) |
title_sort | allele-specific impairment of gjb2 expression by gjb6 deletion del(gjb6-d13s1854) |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126855/ https://www.ncbi.nlm.nih.gov/pubmed/21738759 http://dx.doi.org/10.1371/journal.pone.0021665 |
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