Detection of a Novel Missense Mutation in Atrichia with Papular Lesions

In 2011, researchers discovered a novel missense mutation in the hairless (HR) gene in a Korean patient with Atrichia with Papular Lesions (APL), a condition causing early total hair loss and papular lesions. The study included 11 patients with presumed Alopecia Universalis (AU) who were unresponsive to treatment, and 50 healthy controls. The mutation, a G-to-A transition at nucleotide position 191 in exon 5 of the HR gene, resulted in a glycine to glutamate substitution (G64E) and was absent in the controls, other AU patients, and unaffected family members, except for the patient's mother and maternal grandfather who were heterozygous carriers. The study also noted a new clinical sign of APL, which are follicular hypopigmented macules, and suggested that isolated cases of APL might be more common than previously thought. It recommended HR gene testing for children with presumed AU who do not respond to standard treatments. The study highlighted the need for comprehensive HR gene sequencing for accurate APL diagnosis and suggested three possible explanations for the proband's homozygosity: non-paternity, a large heterozygous deletion in the father, or a spontaneous mutation.