Is the Loose Anagen Hair Syndrome a Keratin Disorder?

Chapalain, Valérie; Winter, Hermelita; Langbein, Lutz; Roy, Jean-Michel Le; Labrèze, Christine; Nikolić, Miloš; Schweizer, Jürgen; Taı̈eb, Alain

doi:10.1001/archderm.138.4.501

Cited by 73 publications

(67 citation statements)

References 23 publications

(42 reference statements)

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“…The missense variant in KRT75 led to a dose-dependent decrease in the hardness of inner enamel, where organic material is more Association with a second rarer missense polymorphism in KRT75 (rs2232398) leading to a glutamate-to-lysine substitution at position 337 (E337K) was shown previously for loose anagen hair syndrome (24). In our cohort, this polymorphism was observed in 1% of the samples and was associated with increased caries in children only (Supplemental Table 2).…”

Section: E337ksupporting

confidence: 66%

Hair keratin mutations in tooth enamel increase dental decay risk

Duverger¹,

O’Hara²,

Shaffer³

et al. 2014

J. Clin. Invest.

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B r i e f r e p o r t5hair in the facial area upon shaving, is associated with a polymorphism (rs2232387) in the KRT75 gene and more prevalent in AfricanAmericans due to the curly nature of their hair (23). This G-to-A missense mutation (KRT75 GA or KRT75 AA genotypes) leads to an alanine-to-threonine substitution at position 161 (A161T) in a highly conserved region of the 1A α-helical segment of KRT75 ( Figure 1E). To determine whether the KRT75 A161T mutation had clinical impact on enamel function, we tested the genetic association between the KRT75 polymorphism (rs2232387) and tooth decay assessed as dental caries experience in the primary dentition of 386 children (mixed European descent, 6-12 years) and permanent dentition of 706 adults (mixed European descent, 25-50 years). The missense A allele of rs2232387, which was observed in 23% of the samples, was associated with a higher number of carious tooth surfaces in adults but not children ( Figure 1F and Supplemental Table 1).We investigated the expression pattern of KRT75 in mouse enamel organ and in mature human enamel. KRT75 was expressed by mouse ameloblasts at the secretory stage (Supplemental Figure 2A) and detected in the tufts and rod sheaths of mature human enamel ( Figure 1, B and C). Interestingly, until enamel matrix proteins were identified, enamel was thought to be a keratinized structure, like hair and nail, with an extreme degree of mineralization (18,19). Here, we show that a subset of hair keratins is expressed by ameloblasts, and we demonstrate that KRT75 is incorporated into the tufts and rod sheaths in mature enamel. Since keratins are not secreted proteins, their deposition in enamel may be related to the retention of cell fragments at the periphery of the rods (20).Mutations in hair keratins have been reported in various human pathological conditions (21, 22). Among them, pseudofolliculitis barbae, a hair disorder characterized by the formation of ingrown (F) Genetic association between the rs2232387 polymorphism and caries experience in primary and permanent dentition. Pie charts show allelic distribution of the rs2232387 polymorphism measured on 706 adults and 386 children. Graphs show measure of caries experience for each genotype: left, number of tooth surfaces with untreated decay (DS and ds); center, number of decayed, missing due to decay, and filled surfaces (DMFS and dfs); right, partial DMFS and dfs indices limited to the molars and premolars pit and fissure (PF and pf) surfaces. etched tooth samples sectioned in the plane transecting the enamel rods revealed that the distribution and characteristic keyhole shape of the rods were altered in individuals carrying the variant A allele (Figure 2A). Tufts and rod sheaths isolated from patients with the KRT75 GA or KRT75 AA genotype appeared disorganized ( Figure 2B), and the distribution pattern of KRT75 was highly disrupted ( Figure 2C). This was further corroborated by transmission electron microscopy analysis ( Figure 2D). These results suggest that epithelial hair keratins s...

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Section: E337ksupporting

confidence: 66%

Hair keratin mutations in tooth enamel increase dental decay risk

Duverger¹,

O’Hara²,

Shaffer³

et al. 2014

J. Clin. Invest.

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“…The companion layer is composed of thin long cells adjacent to the IRS, whereas the K6 + niche (and catagen K6 + ) cells are cuboidal (Hsu et al, 2011). Although they exhibit morphological differences, both layers remain adjacent to the ORS and appear to serve anchorage functions (Hsu et al, 2011;Chapalain et al, 2002). However, although the companion layer and K6 + niche cells share some gene expression characteristics, our data demonstrate that the K6 protein-expressing companion layer is not the source of the K6 + niche cells in telogen.…”

Section: Hopx Expression Defines a Previously Unrecognized Progenitormentioning

confidence: 99%

Hopx expression defines a subset of multipotent hair follicle stem cells and a progenitor population primed to give rise to K6+ niche cells

et al. 2013

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SUMMARYThe mammalian hair follicle relies on adult resident stem cells and their progeny to fuel and maintain hair growth throughout the life of an organism. The cyclical and initially synchronous nature of hair growth makes the hair follicle an ideal system with which to define homeostatic mechanisms of an adult stem cell population. Recently, we demonstrated that Hopx is a specific marker of intestinal stem cells. Here, we show that Hopx specifically labels long-lived hair follicle stem cells residing in the telogen basal bulge. Hopx + cells contribute to all lineages of the mature hair follicle and to the interfollicular epidermis upon epidermal wounding.Unexpectedly, our analysis identifies a previously unappreciated progenitor population that resides in the lower hair bulb of anagenphase follicles and expresses Hopx. These cells co-express Lgr5, do not express Shh and escape catagen-induced apoptosis. They ultimately differentiate into the cytokeratin 6-positive (K6) inner bulge cells in telogen, which regulate the quiescence of adjacent hair follicle stem cells. Although previous studies have suggested that K6 + cells arise from Lgr5-expressing lower outer root sheath cells in anagen, our studies indicate an alternative origin, and a novel role for Hopx-expressing lower hair bulb progenitor cells in contributing to stem cell homeostasis.

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“…9 The patient who responded to minoxidil within 3 months of treatment in this study had many anagen hairs and tapered ends on her trichogram in addition to ruffled cuticles. Together, our conclusions about LAHS herein and the reported characteristics of other common nonscarring hair disorders in children, including alopecia areata, telogen effluvium, androgenetic alopecia, and trichotillomania (Table 3), 13,[31][32][33][34][35][36] should well equip the practitioner to make an appropriate diagnosis of alopecia.…”

Section: Commentmentioning

confidence: 64%