Homozygous Dominant Missense Mutation in Keratin 17 Leads to Alopecia in Addition to Severe Pachyonychia Congenita

This study identified that homozygous dominant missense mutations in the keratin 17 (KRT17) gene led to severe pachyonychia congenita (PC) and alopecia, a novel association with PC. In two families, individuals with homozygous mutations (p.Asn92Ser and p.Arg94Cys) exhibited severe PC symptoms and significant hair loss, while heterozygous family members had milder symptoms. The research suggested that the increased dosage of mutant K17 in homozygotes might cause hair abnormalities due to its critical role in hair follicle function. These findings underscored the importance of genetic testing for such mutations in PC patients with alopecia.