Variant in Central Centrifugal Cicatricial Alopecia.

Clicks: 175
ID: 33684
2019
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #144 of 183 articles by views in The New England journal of medicine

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 183 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Central centrifugal cicatricial alopecia (CCCA) is the most common form of scarring alopecia among women of African ancestry. The disease is occasionally observed to affect women in families in a manner that suggests an autosomal dominant trait and usually manifests clinically after intense hair grooming. We sought to determine whether there exists a genetic basis of CCCA and, if so, what it is.We used exome sequencing in a group of women with alopecia (discovery set), compared the results with those in a public repository, and applied other filtering criteria to identify candidate genes. We then performed direct sequencing to identify disease-associated DNA variations and RNA sequencing, protein modeling, 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.In the discovery set, which included 16 patients, we identified one splice site and three heterozygous missense mutations in in 5 patients (31%). (The approximate prevalence of the disease is up to 5.6%.) encodes peptidyl arginine deiminase, type III (PADI3), an enzyme that post-translationally modifies other proteins that are essential to hair-shaft formation. All three CCCA-associated missense mutations in affect highly conserved residues and are predicted to be pathogenic; protein modeling suggests that they result in protein misfolding. These mutations were found to result in reduced PADI3 expression, abnormal intracellular localization of the protein, and decreased enzymatic activity - findings that support their pathogenicity. Immunofluorescence staining showed decreased expression of PADI3 in biopsy samples of scalp skin obtained from patients with CCCA. We then directly sequenced in an additional 42 patients (replication set) and observed genetic variants in 9 of them. A post hoc analysis of the combined data sets showed that the prevalence of mutation was higher among patients with CCCA than in a control cohort of women of African ancestry (P = 0.002 by the chi-square test; P = 0.006 by Fisher's exact test; and after adjustment for relatedness of persons, P = 0.03 and P = 0.04, respectively).Mutations in , which encodes a protein that is essential to proper hair-shaft formation, were associated with CCCA. (Funded by the Ram Family Foundation and others.).
Reference Key
malki2019variantthe Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Malki, Liron;Sarig, Ofer;Romano, Maria-Teresa;Méchin, Marie-Claire;Peled, Alon;Pavlovsky, Mor;Warshauer, Emily;Samuelov, Liat;Uwakwe, Laura;Briskin, Valeria;Mohamad, Janan;Gat, Andrea;Isakov, Ofer;Rabinowitz, Tom;Shomron, Noam;Adir, Noam;Simon, Michel;McMichael, Amy;Dlova, Ncoza C;Betz, Regina C;Sprecher, Eli;
Journal The New England journal of medicine
Year 2019
DOI
10.1056/NEJMoa1816614
URL
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.