PADI3 Enzyme Mutation Could Be Genetic Element of CCCA Hair Loss

Central Centrifugal Cicatricial Alopecia (CCCA) is a common form of scarring hair loss that affects women of African descent. A 2016 study found that almost half of all African American women have experienced this condition.

Although it is linked to certain intense hairstyling practices - hence it also being known as Hot Comb Alopecia - and inflammation, CCCA has long been suspected of also having a genetic element.

The hallmark of this form of cicatricial alopecia is the shape the hair loss takes; starting in the middle of the scalp, it gradually radiates outwards at either side, forming an increasingly large almond shape.

Researchers in Israel have discovered what they believe may be the root of this genetic constituent: a mutation in the enzyme peptidyl arginine deiminase, type III (PADI3).

Small but thorough study

The potential breakthrough findings were published in the New England Journal of Medicine on 13th February 2019, and reveal it to be a small but in-depth study.

Details explain how a 'discovery group' of 16 patients with CCCA was compared to filtered results from a public database. Study authors from the Tel Aviv Medical Centre's Department of Dermatology, explored these, as follows:

"We then performed direct sequencing to identify disease-associated DNA variations and RNA sequencing, protein modelling, immunofluorescence staining, immunoblotting, and an enzymatic assay to evaluate the consequences of potential etiologic mutations. We used a replication set that consisted of women with CCCA to confirm the data obtained with the discovery set."

What transpired was that the PADI3 enzyme is able to modify other proteins "essential to hair shaft formation". Women with decreased PADI3 and PADI3 mutations, as noted from scalp biopsy samples, were more likely to have CCCA than other women with the same Afro hair type who did not show this genetic quirk.

Area of current research

Whether you call it Central Centrifugal Cicatricial Alopecia, Hot Comb Alopecia or Follicular Degeneration Syndrome (FDS), this form of hair loss has recently come under scrutiny from the medical and pharmaceutical communities, with a number of projects exploring its pathogenesis, as others aim to find a suitable, effective treatment.

The fact this study was, in part, funded by a L’Oreal African Hair and Skin Research grant may suggest the cosmetics giant is also considering developing products for people with this condition.

Currently, Follicular Degeneration Syndrome treatment may be possible when the condition is caught early.

Once the scarring sets in, however, there are few options for hair regrowth, meaning potentially permanent hair loss, though surgical intervention in the form of a hair transplant may be possible.

This is decided very much on a case by case basis given the many variables involved, including the extent of the scalp that is affected, the amount and quality of donor hair the patient has, and whether the scalp is likely to respond well to the new grafts.

Anyone concerned about unusual levels or patterns of hair loss should consult a specialist in order to obtain a timely diagnosis. It is the case with most hair loss conditions that, the earlier the better when starting treatment. Therefore, finding out what you are dealing with as quickly as possible gives you time to explore your options before deciding on the one you feel most comfortable with.