Key result
Sequencing of the exonic and splice site regions of four desmosomal genes associated with human ARVC did not identify a causative mutation for arrhythmogenic right ventricular cardiomyopathy in Boxers.
Case-Control (n=12)
Yes
Mutations in the 4 desmosomal genes associated with human ARVC do not appear to be causative for ARVC in Boxers.
No desmosomal mutations found in Boxer ARVC; leaves open alternative genetic causes and precludes direct translation of human panels.
OBJECTIVE: To sequence the exonic and splice site regions of the 4 desmosomal genes associated with the human form of familial arrhythmogenic right ventricular cardiomyopathy (ARVC) in Boxers with ARVC and identify a causative mutation. ANIMALS: 10 unrelated Boxers with ARVC and 2 unaffected Labrador Retrievers (control dogs). PROCEDURES: Exonic and splice site regions of the 4 genes encoding the desmosomal proteins plakophilin-2, plakoglobin, desmoplakin, and desmoglein-2 were sequenced. Sequences were compared for nucleotide sequence changes between affected dogs and the published sequences for clinically normal dogs and between affected dogs and the control dogs. Base-pair changes were considered to be causative for ARVC if they were detected in an affected dog but not in unaffected dogs, and if they involved a conserved amino acid and changed that amino acid to one of a different polarity, acid-base status, or structure. RESULTS: A causative mutation for ARVC in Boxers was not identified, although single nucleotide polymorphisms were detected in some affected dogs within exon 3 of the plakophilin-2 gene; exon 3 of the plakoglobin gene; exons 3 and 7 of the desmoglein-2 gene; and exons 6, 14, 15, and 24 of the desmoplakin gene. None of these changed the amino acid of the respective protein. CONCLUSIONS AND CLINICAL RELEVANCE: Mutations within the desmosomal genes associated with the development of ARVC in humans do not appear to be causative for ARVC in Boxers. Genomewide scanning for genetic loci of interest in dogs should be pursued.
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Meurs et al. (2007) conducted a case-control in Arrhythmogenic right ventricular cardiomyopathy (ARVC) (n=12). Desmosomal gene mutations (plakophilin-2, plakoglobin, desmoplakin, desmoglein-2) vs. Unaffected Labrador Retrievers and published normal canine sequences was evaluated on Identification of a causative mutation in the exonic and splice site regions of 4 desmosomal genes. Sequencing of the exonic and splice site regions of four desmosomal genes associated with human ARVC did not identify a causative mutation for arrhythmogenic right ventricular cardiomyopathy in Boxers.
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