BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an 
autosomal dominant heart muscle disorder that causes arrhythmia, heart failure, 
and sudden death. Previously we mapped the genetic locus for the triad of 
autosomal recessive ARVC, palmoplantar keratoderma, and woolly hair (Naxos 
disease) to chromosome 17q21, in which the gene for plakoglobin is encoded. This 
protein is a key component of desmosomes and adherens junctions, and is 
important for the tight adhesion of many cell types, including those in the 
heart and skin.
METHODS: We studied 19 individuals with Naxos disease, as well as unaffected 
family members and unrelated individuals from the neighbouring Greek islands of 
Naxos and Milos. Gene sequence was determined by reverse transcriptase PCR from 
RNA isolated from the skin of an affected individual and mutations in other 
cases were confirmed by restriction-enzyme analysis.
FINDINGS: A homozygous 2 base pair deletion in the plakoglobin gene was 
identified only in the 19 affected individuals. This deletion caused a 
frameshift and premature termination of the protein, which was shown by western 
blot analysis. 29 clinically unaffected family members were heterozygous for the 
mutation; 20 unrelated individuals from Naxos and 43 autosomal dominant ARVC 
probands were homozygous for the normal allele.
INTERPRETATION: The finding of a deletion in plakoglobin in ARVC suggests that 
the proteins involved in cell-cell adhesion play an important part in 
maintaining myocyte integrity, and when junctions are disrupted, cell death, and 
fibrofatty replacement occur. Therefore, the discovery of a mutation in a 
protein with functions in maintaining cell junction integrity has important 
implications for other dominant forms of ARVC, related cardiomyopathies, and 
other cutaneous diseases.