Desmosomal gene evaluation in Boxers with arrhythmogenic right ventricular cardiomyopathy.
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.


METHODS
10 unrelated Boxers with ARVC and 2 unaffected Labrador Retrievers (control dogs).


METHODS
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
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.
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
Kathryn M
KM
Meurs
Martina M
MM
Ederer
Joshua A
JA
Stern
D000818:Animals; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000235:genetics / Q000662:veterinary*; D001483:Base Sequence; D051301:Desmoglein 2 / Q000235:genetics; D051180:Desmoplakins / Q000235:genetics; D003896:Desmosomes / Q000235:genetics*; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D008297:Male; D005810:Multigene Family; D051191:Plakophilins / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D051185:gamma Catenin / Q000235:genetics
D051301:Desmoglein 2; D051180:Desmoplakins; D051191:Plakophilins; D022821:RNA Splice Sites; D051185:gamma Catenin