A Homozygous Nonsense Mutation in the Zinc-Finger Domain of the Human Hairless Gene Underlies Congenital Atrichia

The study identified a homozygous nonsense mutation in the zinc-finger domain of the human hairless gene as the cause of congenital atrichia, a rare form of total alopecia inherited in an autosomal recessive pattern. This mutation, observed in a Japanese family, results in the absence of mRNA and functional protein due to nonsense-mediated mRNA decay, leading to complete hair loss without other physical or developmental abnormalities. Similar mutations were reported in families from Pakistan, Ireland, and Israel, indicating a mutation cluster in the zinc-finger domain. Despite high expression of the hairless gene in the brain, no neurological defects were noted. The hairless protein functions as a transcriptional corepressor essential for transitioning to the first adult hair cycle, and its absence causes premature apoptosis of hair matrix cells, disrupting hair growth. The study emphasized the hairless gene's role in maintaining cell process balance in hair follicles, with its dysfunction resulting in inherited alopecia.