Deciphering the Pathogenesis of Central Centrifugal Cicatricial Alopecia
September 2019
TLDR Mutations in the PADI3 gene may cause central centrifugal cicatricial alopecia in women of African ancestry.
Central centrifugal cicatricial alopecia (CCCA) was identified as the most common form of scarring alopecia among women of African ancestry, with a prevalence of 2.7%-5.6%. The study aimed to identify genetic risk variants for CCCA and used whole exome sequencing in 16 patients, discovering one splice site and three heterozygous missense mutations in the PADI3 gene. These mutations were predicted to be pathogenic, affecting highly conserved residues and resulting in protein misfolding, reduced PADI3 expression, abnormal protein localization, and decreased enzymatic activity. Immunofluorescence staining confirmed decreased PADI3 expression in CCCA patients' scalp skin. In a replication set of 42 patients, pathogenic variants were found in 24% of all CCCA patients, suggesting that mutations in PADI3, which is crucial for hair shaft formation, may lead to CCCA.