Arrhythmogenic right ventricular cardiomyopathy type 6 (ARVC6): support for the locus assignment, narrowing of the critical region and mutation screening of three candidate genes

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dc.contributor.authorMatolweni, Luzukoen_ZA
dc.contributor.authorBardien, Sorayaen_ZA
dc.contributor.authorRebello, Georgeen_ZA
dc.contributor.authorOppon, Ekowen_ZA
dc.contributor.authorMunclinger, Miroslaven_ZA
dc.contributor.authorRamesar, Rajkumaren_ZA
dc.contributor.authorWatkins, Hughen_ZA
dc.contributor.authorMayosi, Bonganien_ZA
dc.date.accessioned2015-10-12T10:52:17Z
dc.date.available2015-10-12T10:52:17Z
dc.date.issued2006en_ZA
dc.description.abstractBACKGROUND:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable disorder characterized by progressive degeneration of right ventricular myocardium, arrhythmias and an increased risk of sudden death at a young age. By linkage analysis, ARVC type 6 was previously mapped to a 10.6 cM region on chromosome 10p12-p14 in a large North American kindred. To date, the genetic defect that causes ARVC6 has not been identified. METHODS: We identified a South African family of 13 members with ARVC segregating as an autosomal dominant disorder. The diagnosis of ARVC was based on international diagnostic criteria. All available family members were genotyped with microsatellite markers at six known ARVC loci, and positional candidate gene screening was performed. RESULTS: Genetic linkage and haplotype analysis provided lod scores that are highly suggestive of linkage to the ARVC6 locus on chromosome 10p12-p14, and the narrowing of the critical region to ~2.9 Mb. Two positional candidate genes (ITG8 and FRMD4A) were screened in which defects could possibly disrupt cell-cell adhesion. A non-positional candidate gene with apoptosis inducing properties, LAMR1P6 (laminin receptor 1 pseudogene 6) was also screened. Direct sequencing of DNA from affected individuals failed to detect disease-causing mutations in the exonic sequences of the three genes investigated. CONCLUSION: The narrowing of the ARVC6 critical region may facilitate progress towards the identification of the gene that is involved in ARVC. Identification of the causative genes for ARVC will contribute to the understanding of the pathogenesis and management of this poorly understood condition.en_ZA
dc.identifier.apacitationMatolweni, L., Bardien, S., Rebello, G., Oppon, E., Munclinger, M., Ramesar, R., ... Mayosi, B. (2006). Arrhythmogenic right ventricular cardiomyopathy type 6 (ARVC6): support for the locus assignment, narrowing of the critical region and mutation screening of three candidate genes. <i>BMC Medical Genetics</i>, http://hdl.handle.net/11427/14169en_ZA
dc.identifier.chicagocitationMatolweni, Luzuko, Soraya Bardien, George Rebello, Ekow Oppon, Miroslav Munclinger, Rajkumar Ramesar, Hugh Watkins, and Bongani Mayosi "Arrhythmogenic right ventricular cardiomyopathy type 6 (ARVC6): support for the locus assignment, narrowing of the critical region and mutation screening of three candidate genes." <i>BMC Medical Genetics</i> (2006) http://hdl.handle.net/11427/14169en_ZA
dc.identifier.citationMatolweni, L. O., Bardien, S., Rebello, G., Oppon, E., Munclinger, M., Ramesar, R., ... & Mayosi, B. M. (2006). Arrhythmogenic right ventricular cardiomyopathy type 6 (ARVC6): support for the locus assignment, narrowing of the critical region and mutation screening of three candidate genes. BMC medical genetics, 7(1), 29.en_ZA
dc.identifier.ris TY - Journal Article AU - Matolweni, Luzuko AU - Bardien, Soraya AU - Rebello, George AU - Oppon, Ekow AU - Munclinger, Miroslav AU - Ramesar, Rajkumar AU - Watkins, Hugh AU - Mayosi, Bongani AB - BACKGROUND:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable disorder characterized by progressive degeneration of right ventricular myocardium, arrhythmias and an increased risk of sudden death at a young age. By linkage analysis, ARVC type 6 was previously mapped to a 10.6 cM region on chromosome 10p12-p14 in a large North American kindred. To date, the genetic defect that causes ARVC6 has not been identified. METHODS: We identified a South African family of 13 members with ARVC segregating as an autosomal dominant disorder. The diagnosis of ARVC was based on international diagnostic criteria. All available family members were genotyped with microsatellite markers at six known ARVC loci, and positional candidate gene screening was performed. RESULTS: Genetic linkage and haplotype analysis provided lod scores that are highly suggestive of linkage to the ARVC6 locus on chromosome 10p12-p14, and the narrowing of the critical region to ~2.9 Mb. Two positional candidate genes (ITG8 and FRMD4A) were screened in which defects could possibly disrupt cell-cell adhesion. A non-positional candidate gene with apoptosis inducing properties, LAMR1P6 (laminin receptor 1 pseudogene 6) was also screened. Direct sequencing of DNA from affected individuals failed to detect disease-causing mutations in the exonic sequences of the three genes investigated. CONCLUSION: The narrowing of the ARVC6 critical region may facilitate progress towards the identification of the gene that is involved in ARVC. Identification of the causative genes for ARVC will contribute to the understanding of the pathogenesis and management of this poorly understood condition. DA - 2006 DB - OpenUCT DO - 10.1186/1471-2350-7-29 DP - University of Cape Town J1 - BMC Medical Genetics LK - https://open.uct.ac.za PB - University of Cape Town PY - 2006 T1 - Arrhythmogenic right ventricular cardiomyopathy type 6 (ARVC6): support for the locus assignment, narrowing of the critical region and mutation screening of three candidate genes TI - Arrhythmogenic right ventricular cardiomyopathy type 6 (ARVC6): support for the locus assignment, narrowing of the critical region and mutation screening of three candidate genes UR - http://hdl.handle.net/11427/14169 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14169
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2350-7-29
dc.identifier.vancouvercitationMatolweni L, Bardien S, Rebello G, Oppon E, Munclinger M, Ramesar R, et al. Arrhythmogenic right ventricular cardiomyopathy type 6 (ARVC6): support for the locus assignment, narrowing of the critical region and mutation screening of three candidate genes. BMC Medical Genetics. 2006; http://hdl.handle.net/11427/14169.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentDivision of Cardiologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceBMC Medical Geneticsen_ZA
dc.source.urihttp://www.biomedcentral.com/bmcmedgenet/en_ZA
dc.subject.otherArrhythmogenic right ventricular cardiomyopathyen_ZA
dc.titleArrhythmogenic right ventricular cardiomyopathy type 6 (ARVC6): support for the locus assignment, narrowing of the critical region and mutation screening of three candidate genesen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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