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Allele-specific impairment of GJB2 expression by GJB6 deletion del(GJB6-D13S1854).
Rodriguez-Paris, Juan; Tamayo, Marta L; Gelvez, Nancy; Schrijver, Iris.
Afiliação
  • Rodriguez-Paris J; Department of Pathology, Stanford University School of Medicine, Stanford, California, United States of America.
PLoS One ; 6(6): e21665, 2011.
Article em En | MEDLINE | ID: mdl-21738759
ABSTRACT
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Conexinas Limite: Humans Idioma: En Ano de publicação: 2011 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Conexinas Limite: Humans Idioma: En Ano de publicação: 2011 Tipo de documento: Article