Pathogenic Variants Affecting Peptidyl Arginine Deiminase 3 and Its Major Substrates Underlie Central Centrifugal Cicatricial Alopecia

This study investigates the genetic basis of central centrifugal cicatricial alopecia (CCCA), a common form of scarring alopecia in women of African descent, by analyzing whole-exome sequences from 75 patients. Researchers identified 9 pathogenic variants in the PADI3 gene, including 4 previously unreported missense variants that disrupt protein function. Additionally, variants in the S100A3 and TCHH genes, which encode substrates of PADI3, were found. These variants affect hair shaft integrity by reducing citrullination and altering protein expression and localization. The findings enhance understanding of CCCA's genetic mechanisms and may guide future genetic testing and therapies.