Atrichia caused by mutations in the vitamin D receptor gene is a phenocopyof generalized atrichia caused by mutations in the hairless gene

Generalized atrichia with papules is a rare disorder characterized by loss of hair shortly after birth and development of cutaneous cysts. Mutations i n the hairless gene (HR) cause this phenotype in both mouse and human. Here we present a case of atrichia with papules in a patient with a normal HAIR LESS gene but with mutations in both alleles of the VITAMIN D RECEPTOR. The patient exhibited vitamin D resistant rickets, which was confirmed by an a bsent response of her fibroblasts to 1,25-dihydroxyvitamin D-3 in vitro. Si milar to individuals with HAIRLESS mutations, her skin showed an absence of normal hair follicles and the presence of follicular remnants and cysts. T he cyst epithelium contained keratin-15- and keratin-17-positive cells sugg esting derivation from the hair follicle bulge and the presence of epitheli al stem cells. Although hair loss has been reported in association with her editary vitamin D resistant rickets, we now characterize this alopecia as c linically and pathologically indistinguishable from generalized atrichia wi th papules, which was previously thought to be caused only by mutations in HAIRLESS. These findings suggest that VDR and HR, which are both zinc finge r proteins, may be in the same genetic pathway that controls postnatal cycl ing of the hair follicle.