Genome Scans Provide Evidence for Keloid Susceptibility Loci on Chromosomes 2q23 and 7p11

Abstract

Keloids are proliferative fibrous growths that result from an excessive tissue response to skin trauma. They often occur sporadically, but in some families a genetic predisposition to keloids has been observed. Here we studied two families with an autosomal dominant inheritance pattern of keloids. One African-American family showed a high degree of variability in the extent of keloid formation between family members, whereas the second family from Japan showed a pattern of full penetrance and the formation of only small keloids. We performed a genome-wide linkage search for genes predisposing to keloid formation in these two families. We identified linkage to chromosome 2q23 (maximal two-point LOD score of 3.01) for the Japanese family. The African-American family showed evidence for a keloid susceptibility locus on chromosome 7p11 (maximal two-point LOD score of 3.16). The observed locus heterogeneity in autosomal dominant keloid disease is consistent with the clinical heterogeneity of this scarring disorder. Dense microsatellite analysis in these two loci was performed and candidate genes were identified. This study provides the first genetic evidence for keloid susceptibility loci and serves as a basis for the identification of responsible genes.