Variant PADI3 in Central Centrifugal Cicatricial Alopecia

February 2019 in “ The New England Journal of Medicine ”

Liron Malki, Ofer Sarig, Maria-Teresa Romano, Marie-Claire Méchin, A. Peled, Mor Pavlovsky, Emily Warshauer, Liat Samuelov, Laura N Uwakwe, Valeria Briskin, Janan Mohamad, Andrea Gat, Ofer Isakov, Tom Rabinowitz, Noam Shomron, Noam Adir, Michel Simon, Amy J. McMichael, Ncoza C. Dlova, Regina C. Betz, Eli Sprecher

PADI3 Central Centrifugal Cicatricial Alopecia CCCA scarring alopecia hair-shaft formation protein misfolding intracellular localization enzymatic activity

TLDR Mutations in the PADI3 gene are linked to a higher risk of scarring hair loss in women of African descent.

The study from February 28, 2019, found that mutations in the PADI3 gene are associated with Central Centrifugal Cicatricial Alopecia (CCCA), a form of scarring alopecia prevalent among women of African ancestry. The research included a total of 58 patients, with 16 in the discovery set and 42 in the replication set. In the discovery set, 5 out of 16 patients (31%) had PADI3 mutations, while in the replication set, 9 out of 42 patients had genetic variants in PADI3. The mutations were linked to decreased PADI3 expression, protein misfolding, abnormal intracellular localization, and reduced enzymatic activity, which are essential for proper hair-shaft formation. The study concluded that the prevalence of PADI3 mutation was significantly higher in patients with CCCA compared to a control group, suggesting that these damaging genetic variants contribute to the higher prevalence of CCCA in women of African ancestry.

View this study on nejm.org →

Discuss this study in the Community →

Research cited in this study

13 / 13 results

research Crosslinking Between Trichocyte Keratins and Keratin Associated Proteins

13 citations , January 2018 in “Advances in experimental medicine and biology”

research Central Centrifugal Cicatricial Alopecia: New Insights and a Call for Action

27 citations , September 2017 in “Journal of Investigative Dermatology Symposium Proceedings”

Hair loss in black women needs more research, early intervention, and community education.

research Mutations in Three Genes Encoding Proteins Involved in Hair Shaft Formation Cause Uncombable Hair Syndrome

119 citations , November 2016 in “American journal of human genetics”

Mutations in three genes cause Uncombable Hair Syndrome, leading to frizzy hair that can't be combed flat.

research Primary Cicatricial Alopecia

65 citations , November 2016 in “Journal of The American Academy of Dermatology”

The document concludes that early recognition and treatment of primary cicatricial alopecia is crucial to prevent permanent hair loss.

research Factors Affecting the Severity of Central Centrifugal Cicatricial Alopecia

29 citations , January 2016 in “International Journal of Dermatology”

Longer hair loss leads to more severe CCCA; early treatment and avoiding damaging hairstyles help regrowth.

research Central Hair Loss in African American Women: Incidence and Potential Risk Factors

76 citations , November 2010 in “Journal of The American Academy of Dermatology”

Some African American women's central scalp hair loss is linked to genetics and past fungal scalp infections, with more research needed on other causes.

research Central Scalp Alopecia Photographic Scale in African American Women

46 citations , July 2008 in “Dermatologic Therapy”

A scale was made to measure hair loss severity in African American women.

research Human Hair Growth Deficiency Is Linked to a Genetic Defect in the Phospholipase Gene LIPH

194 citations , November 2006 in “Science”

A genetic mutation in the LIPH gene causes hair loss and growth defects.

research Peptidylarginine Deiminase Isoforms Are Differentially Expressed in Anagen Hair Follicles and Other Human Skin Appendages

71 citations , June 2005 in “Journal of Investigative Dermatology”

PAD enzymes play a key role in hair growth and structure.

research Human Peptidylarginine Deiminase Type III: Molecular Cloning and Nucleotide Sequence of the cDNA, Properties of the Recombinant Enzyme, and Immunohistochemical Localization in Human Skin

124 citations , November 2000 in “The journal of investigative dermatology/Journal of investigative dermatology”

PAD3 plays a key role in hair and skin protein structure and may be linked to skin diseases.

research Alopecia Universalis Associated With a Mutation in the Human Hairless Gene

412 citations , January 1998 in “Science”

A mutation in the human hairless gene causes alopecia universalis.

research Uncombable-Hair Syndrome

12 citations , November 1987 in “Pediatric dermatology”

Four children had unmanageable pale blond hair due to uncombable-hair syndrome.

research Hot Comb Alopecia

107 citations , September 1968 in “Archives of Dermatology”

Using hot combs can cause permanent hair loss on the scalp's crown.

Similar Research

6 / 149 results

research Bioactive Compound-Loaded Nanocarriers for Hair Growth Promotion: Current Status and Future Perspectives

October 2023 in “Plants”

Nanocarriers with plant extracts show promise for safe and effective hair growth treatment.

research Central Centrifugal Cicatricial Alopecia: Unraveling the Complexities of a Scarring Hair Disorder

February 2024 in “International journal of medical science and clinical research studies”

CCCA is a scarring hair disorder mainly affecting people of African descent, needing better awareness and treatment.

research SnapshotDx Quiz: May 2022

April 2022 in “Journal of Investigative Dermatology”

Androgenetic alopecia causes hair thinning due to increased androgen activity, treatable with minoxidil and finasteride.

research Recent Advances in Understanding of the Etiopathogenesis, Diagnosis, and Management of Hair Loss Diseases

May 2023 in “Journal of Clinical Medicine”

New understanding and treatments for hair loss are improving, but more research is needed.

research Pili Trianguli Et Canaliculati as a Phenotypic Subtype in Patients with Central Centrifugal Cicatricial Alopecia: A Scanning Electron Microscopy Study

2 citations , May 2020 in “Journal of the American Academy of Dermatology”

Hair shaft changes may be linked to CCCA, but their role is unclear.

research Using Scanning Electron Microscopy to Elucidate the Role of Hair Shaft Malformation in the Pathogenesis of Central Centrifugal Cicatricial Alopecia

June 2020 in “Journal of Investigative Dermatology”

Hair shaft malformation contributes to Central Centrifugal Cicatricial Alopecia.