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Gene Mutations May Predispose Women to Alopecia Subtype

Key clinical point: Women with central centrifugal cicatricial alopecia (CCCA) were more likely to have a mutation of the PAD13 gene than unaffected women.

Major finding: Researchers identified six mutations in PAD13 that appeared in 24% of 58 women with CCCA.

Study details: The data come from 58 adult women with African ancestry who had a diagnosis of CCCA.

Disclosures: The study was supported in part by a grant to Eli Sprecher, MD, PhD, from the Ram Family Foundation and a grant to Dr. Sprecher and Regina C. Betz, MD, from the German-Israeli Foundation, a L’Oreal African Hair and Skin Research grant to Ncoza C. Dlova, a research grant from the Skin of Color Society to Amy McMichael, MD, and the Deutsche Forschungsgemeinschaft–funded Cluster of Excellence ImmunoSensation grant to Dr. Betz. Several other researchers – but not all – reported numerous financial disclosures from pharmaceutical and technology companies and universities and organizations.


Malki L et al. N Engl J Med. 2019 Feb 13. doi: 10.1056/NEJMoa1816614.


Central centrifugal cicatricial alopecia (CCCA) is characterized by hair loss with rapid, progressive, and permanent hair follicle destruction, Jouni Uitto, MD, PhD, wrote in an accompanying editorial.

The current study showed six distinct genetic mutations in PAD13, a gene that allows normal hair follicle development, in 14 of 58 women with CCCA. The researchers also found that genes involved in hair shaft formation were expressed differently in women with CCCA than in unaffected women. Dr. Uitto wrote. Thus, variants in other genes likely contribute to CCCA pathogenesis.

“The observations by Malki et al. suggest that PADI3 mutations predispose persons to CCCA, which is then clinically manifested when hairstyling practices damage the hair. Thus, in the familial setting, such practices should be discouraged in both symptomatic and asymptomatic family members.” he wrote.

Dr. Uitto also noted that uncombable hair syndrome, a rare disorder not associated with alopecia or scarring, also has been associated with mutations in PAD13. However, uncombable hair syndrome is most common in children, who usually outgrow the condition, and it appears not to be inherited. “The mutations in PADI3 in these two conditions are distinct, which suggests different pathogenic consequences of specific PADI3 variants on hair development.”

The PAD13 mutations may predispose women to CCCA, but the data do not support screening asymptomatic women, Dr. Uitto wrote.

“The presence of variants in PADI3 in both CCCA and uncombable hair syndrome suggests that this gene has a pleiotropic effect on the determination of hair texture, and the finding holds implications for future development of therapy, such as the restoration of PADI3 activity,” he concluded.

Dr. Uitto is affiliated with the department of dermatology and cutaneous biology at Jefferson Medical College, Philadelphia. This is a summary of his editorial accompanying the article by Malki et al. (New Engl J Med. 2019 Feb 13. doi: 10.1056/NEJMe1900042). He reported no relevant financial disclosures.