Mutations in the Desmoglein 4 Gene Underlie Localized Autosomal Recessive Hypotrichosis with Monilethrix Hairs and Congenital Scalp Erosions

The study identified mutations in the Desmoglein 4 (DSG4) gene as the cause of localized autosomal recessive hypotrichosis (LAH) with monilethrix-like hairs and congenital scalp erosions in three siblings of Iraqi and Iranian origin. These individuals exhibited novel compound heterozygous DSG4 mutations, including a splice-site mutation and a missense mutation affecting a calcium-binding site, leading to reduced DSG4 protein expression and impacting hair follicle differentiation and epidermal adhesion. This research expanded the phenotypic and genotypic spectrum of LAH, underscoring the critical role of DSG4 in maintaining hair and skin integrity and marking the first description of such hair shaft abnormalities in humans.