Desmoglein 4 Mutations Underlie Localized Autosomal Recessive Hypotrichosis in Humans, Mice, and Rats

Abstract

A newly defined form of inherited hair loss, named localized autosomal recessive hypotrichosis (LAH, OMIM 607903), was recently described in the literature and shown to be linked to chromosome 18. A large, intragenic deletion in the desmoglein 4 gene (DSG4) as the underlying mutation in several unrelated families of Pakistani origin. LAH is an autosomal recessive form of hypotrichosis affecting the scalp, trunk, and extremities, and largely sparing the facial, pubic, and axillary hair. Typical hairs are fragile and break easily, leaving short sparse scalp hairs with a characteristic appearance. Using comparative genomics, we also demonstrated that human LAH is allelic with the lanceolate hair (lah) mouse, as well as the lanceolate hair (lah) rat phenotype. Together, these models provide new information about the role of desmosomal cadherins in disease, and serve as in vivo models for functional and mechanistic studies into the role of desmoglein 4 in the skin and hair follicle.