Hypotrichosis with juvenile macular dystrophy is caused by a mutation in CDH3, encoding P-cadherin

Congenital hypotrichosis associated with juvenile macular dystrophy (HJMD; MIM601553) is an autosomal recessive disorder of unknown etiology, characte rized by hair loss heralding progressive macular degeneration and early bli ndness(1,2). We used homozygosity mapping in four consanguineous families t o localize the gene defective in HJMD to 16q22.1. This region contains CDH3 , encoding P-cadherin, which is expressed in the retinal pigment epithelium and hair follicles. Mutation analysis shows in all families a common homoz ygous deletion in exon 8 of CDH3. These results establish the molecular eti ology of HJMD and implicate for the first time a cadherin molecule in the p athogenesis of a human hair and retinal disorder.