Atrichia with Papular Lesions Resulting from a Nonsense Mutation Within the Human Hairless Gene

Abstract

Atrichia with papular lesions is a rare autosomal recessive form of alopecia characterized by hair loss soon after birth and the development during childhood of a diffuse papular rash. We have previously shown that this disorder results from a deleterious mutation in the human hairless gene, a gene also involved in the pathogenesis of a related but clinically distinct form of congenital alopecia, termed alopecia universalis congenita. In this report, we describe a novel nonsense mutation in exon 4 of the human hairless gene in a consanguineous kindred affected with atrichia with papular lesions. This report provides additional evidence for phenotypic heterogeneity among inherited atrichias and for an association between the papular rash of atrichia with papular lesions and nonsense mutations in the human hairless gene.

The co-repressor hairless has a role in epithelial cell differentiation in the skin

“…The Hr gene was identified by mapping the retroviral insertion in the original murine allele (Cachon-Gonzalez et al, 1994;Stoye et al, 1988) and as a thyroid hormone-regulated gene in rat brain (Thompson, 1996). Identification of the human ortholog revealed that mutations in the Hr gene result in congenital hair loss disorders (alopecia universalis, papular atrichia) Cichon et al, 1998;Sprecher et al, 1999). Multiple mutant Hr alleles in both mice and humans show phenotypic variations that can include skin wrinkling and papular rash (Panteleyev et al, 1998b).…”

Hairless and Wnt Signaling: Allies in Epithelial Stem Cell Differentiation

“…17,18 Hr MUTANTS LACK COREPRESSOR ACTIVITY Multiple human alleles of Hr that result in congenital hair loss disorders (alopecia universalis, papular atrichia) have been described, and include both nonsense and missense mutations. 14,[29][30][31][32][33][34] Surprisingly, few of the mutations map to established functional domains (Fig. 1B).…”

Hairless: il s’en est fallu d’un cheveu

“…Thompson. Une première mutation non sens (nt1432 C → T, exon 4) [4] aboutit à un arrêt prématuré de la traduction à l'acide aminé 481. La protéine hairless, si elle est effectivement synthétisée, ne comprendrait que le domaine RD1 et le signal de localisation nucléaire.…”

“…Quelle est la fonction biologique de ce gène ? Le gène hairless est associé à des désordres capillaires congénitaux, comme l'alopecia universalis et l'atrichose papulaire [2,[4][5][6][7][8]. Bien que de nombreux allèles aient été identifiés chez la souris et chez l'homme, un phé-notype commun est observé : après une première phase de croissance normale, le poil (le cheveu) ne repousse pas après sa chute.…”