MRPS18CP2 alleles and DEFA3 absence as putative chromosome 8p23.1 modifiers of hearing loss due to mtDNA mutation A1555G in the 12S rRNA gene

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• dc.contributor.author Ballana Guix, Esterca
• dc.contributor.author Mercader Bigas, Josep Mariaca
• dc.contributor.author Fischel Ghodsian, Nathanca
• dc.contributor.author Estivill, Xavier, 1955-ca
• dc.date.accessioned 2014-12-22T12:59:21Z
• dc.date.available 2014-12-22T12:59:21Z
• dc.date.issued 2007ca
• dc.description.abstract Background: Mitochondrial DNA (mtDNA) mutations account for at least 5% of cases of postlingual, nonsyndromic hearing impairment. Among them, mutation A1555G is frequently found associated with aminoglycoside-induced and/or nonsyndromic hearing loss in families presenting with extremely variable clinical phenotypes. Biochemical and genetic data have suggested that nuclear background is the main factor involved in modulating the phenotypic expression of mutation A1555G. However, although a major nuclear modifying locus was located on chromosome 8p23.1 and regardless intensive screening of the region, the gene involved has not been identified. Methods: With the aim to gain insights into the factors that determine the phenotypic expression of A1555G mutation, we have analysed in detail different genetic and genomic elements on 8p23.1 region (DEFA3 gene absence, CLDN23 gene and MRPS18CP2 pseudogene) in a group of 213 A1555G carriers./n/nResults/nFamily based association studies identified a positive association for a polymorphism on MRPS18CP2 and an overrepresentation of DEFA3 gene absence in the deaf group of A1555G carriers. Conclusion: Although none of the factors analysed seem to have a major contribution to the phenotype, our findings provide further evidences of the involvement of 8p23.1 region as a modifying locus for A1555G 12S rRNA gene mutation.
• dc.description.sponsorship This work was supported by "La Marató de TV3" (993610), "Instituto de Salud Carlos III, FIS-ISCIII" (G03/203, PI052347 and CIBER-CB06/02/0058) and "Generalitat de Catalunya" (2005SGR00008). The Spanish National Genotyping Center (CeGen) is founded by "Genoma España". EB is recipient of a fellowship from "Generalitat de Catalunya" (2003FI00066). JMM was supported by the CRG under project SAF2002-00799 (Spanish Ministry of Science and Education), and by a fellowship of the Danone Institute. NFG acknowledges support from NIH/NIDCD grant RO1DC01402.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Ballana E, Mercader J, Fischel-Ghodsian N, Estivill X. MRPS18CP2 alleles and DEFA3 absence as putative chromosome 8p23.1 modifiers of hearing loss due to mtDNA mutation A1555G in the 12S rRNA gene. BMC Medical Genetics. 2007 Dec;8:81. DOI: 10.1186/1471-2350-8-81ca
• dc.identifier.doi http://dx.doi.org/10.1186/1471-2350-8-81
• dc.identifier.issn 1471-2350ca
• dc.identifier.uri http://hdl.handle.net/10230/23023
• dc.language.iso engca
• dc.publisher BioMed Centralca
• dc.relation.ispartof Medical Genetics. 2007 Dec;8:81
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PN/SAF2002-00799
• dc.rights © 2007 Ballana et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License. http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by/2.0
• dc.subject.other Fenotip
• dc.subject.other ADN
• dc.subject.other Mutació
• dc.title MRPS18CP2 alleles and DEFA3 absence as putative chromosome 8p23.1 modifiers of hearing loss due to mtDNA mutation A1555G in the 12S rRNA geneca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca