BACKGROUND: Ebstein anomaly of the tricuspid valve is a congenital cardiac malformation characterised by downward displacement of the attachment of the septal and posterior leaflets of the tricuspid valve. Canine tricuspid valve malformation (CTVM) is morphologically similar to Ebstein anomaly; familial occurrence of CTVM has been described. Several observations suggest a genetic cause but most cases appear to be sporadic. METHODS: Three purebred Labrador Retriever kindreds enriched for CTVM underwent clinical examination and echocardiography. DNA was extracted from whole blood. Genotyping was carried out using polymorphic repeat markers with an average spacing of 15 cM and polymorphic information content of 0.74. RESULTS: Pedigree analysis identified CTVM segregating as an autosomal dominant trait with reduced penetrance. Genome wide linkage analysis in one kindred identified a CTVM susceptibility locus on dog chromosome 9 (CFA9) with a maximum multipoint lod score of 3.33. The two additional kindreds showed a conserved disease haplotype. CONCLUSIONS: This study identifies a CTVM susceptibility locus on CFA9 and a founder effect in apparently unrelated Labrador Retriever kindreds. These results provide the basis for a positional candidate cloning effort to identify the CTVM disease gene. Identification of the CTVM gene will permit mutation screening of patients with Ebstein anomaly, which should provide additional insights into the genetic programmes of valve development.
BACKGROUND:Ebstein anomaly of the tricuspid valve is a congenital cardiac malformation characterised by downward displacement of the attachment of the septal and posterior leaflets of the tricuspid valve. Caninetricuspid valve malformation (CTVM) is morphologically similar to Ebstein anomaly; familial occurrence of CTVM has been described. Several observations suggest a genetic cause but most cases appear to be sporadic. METHODS: Three purebred Labrador Retriever kindreds enriched for CTVM underwent clinical examination and echocardiography. DNA was extracted from whole blood. Genotyping was carried out using polymorphic repeat markers with an average spacing of 15 cM and polymorphic information content of 0.74. RESULTS: Pedigree analysis identified CTVM segregating as an autosomal dominant trait with reduced penetrance. Genome wide linkage analysis in one kindred identified a CTVM susceptibility locus on dog chromosome 9 (CFA9) with a maximum multipoint lod score of 3.33. The two additional kindreds showed a conserved disease haplotype. CONCLUSIONS: This study identifies a CTVM susceptibility locus on CFA9 and a founder effect in apparently unrelated Labrador Retriever kindreds. These results provide the basis for a positional candidate cloning effort to identify the CTVM disease gene. Identification of the CTVM gene will permit mutation screening of patients with Ebstein anomaly, which should provide additional insights into the genetic programmes of valve development.
Authors: M Breen; S Jouquand; C Renier; C S Mellersh; C Hitte; N G Holmes; A Chéron; N Suter; F Vignaux; A E Bristow; C Priat; E McCann; C André; S Boundy; P Gitsham; R Thomas; W L Bridge; H F Spriggs; E J Ryder; A Curson; J Sampson; E A Ostrander; M M Binns; F Galibert Journal: Genome Res Date: 2001-10 Impact factor: 9.043
Authors: G E Eyster; L Anderson; A T Evans; A Chaffee; G Bender; J Johnston; W Muir; G Blanchard Journal: J Am Vet Med Assoc Date: 1977-04-01 Impact factor: 1.936
Authors: Petra Werner; Michael G Raducha; Ulana Prociuk; Elaine A Ostrander; Richard S Spielman; Ewen F Kirkness; Donald F Patterson; Paula S Henthorn Journal: Hum Genet Date: 2005-02-12 Impact factor: 4.132
Authors: Robert J Sicko; Marilyn L Browne; Shannon L Rigler; Charlotte M Druschel; Gang Liu; Ruzong Fan; Paul A Romitti; Michele Caggana; Denise M Kay; Lawrence C Brody; James L Mills Journal: PLoS One Date: 2016-10-27 Impact factor: 3.240
Authors: Iuliu Scurtu; Flaviu Tabaran; Mircea Mircean; Gavril Giurgiu; Andras Nagy; Cornel Catoi; Dan G Ohad Journal: BMC Vet Res Date: 2017-11-29 Impact factor: 2.741