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Mutations with Hair Shape Phenotypes Abnormalities—The Journal of Cosmetics, Dermatological Sciences and Applications, 2013, 3, 26-34 http://dx.doi.org/10.4236/jcdsa.2013.33A1004 Published Online September 2013 (http://www.scirp.org/journal/jcdsa) Mutations with Hair Shape Phenotypes Abnormalities— The Morphogenetic Waves and Related Diseases Junmin Wang1, Guannan Wang2, Jintao Zhang1* 1Laboratory Animal Center, Zhengzhou University, Zhengzhou, China; 2College of Life Sciences, Henan Agricultural University, Zhengzhou, China. Email: *[email protected] Received June 10th, 2013; revised July 8th, 2013; accepted July 16th, 2013 Copyright © 2013 Junmin Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Hair morphology is one of the most conspicuous features of human variation. The hair follicle has attracted significant attention as a model for the investigation of diverse biological problems. Whereas, very little is known about the genes influencing the morphology and structure of the hair shaft. Curly hair is very common character of hair phenotypes of human, while most congenital curl occurs owing to genetic factors and some are closely related with genetic diseases. This review highlights current related genes reported affecting hair curliness and human diseases which are due to gene mutations. Keywords: Waved Hair; Curly Hair; Gene Mutations; Diseases 1. Introduction and a root that is imbedded in the skin. Its basic compo- nents are keratin (a protein), melanin (a pigment), and A mammal’s pelage is generally one of its first notice- trace quantities of metallic elements [5]. These elements able attributes and is aesthetically pleasing. Moreover, are deposited in the hair during its growth and/or ab- the skin is an essential organ which protects the organism sorbed by the hair from an external environment. After a from invasion of pathogens and chemicals and prevents period of growth, the hair remains in the follicle in a the escape of liquids and nutrients [1]. Its ectodermal resting stage to eventually be sloughed from the body. As appendages, such as hair, feather and tooth, are attractive the place of origin of the hair, the structural change of models for understanding the mechanisms underlying hair follicle could directly cause the change of hair phe- epithelial mesenchymal interactions [2]. notype [6,7]. Hair is composed of terminally differentiated, dead The hair follicle represents an attractive experimental keratinocytes (trichocytes), which are compacted into a system because of its accessibility, dispensability, and fibre of amazing tensile strength, the hair shaft. Hair self-renewal capacity. Owing to its complex but highly morphogenesis and epidermal development are orches- organised architecture, this mini-organ can serve as an trated by an array of cytokines and growth factors [3]. excellent model for investigating aspects of stem cell The presence of hair is characteristic for mammals, in biology, cell lineage specification, cell differentiation, which it exerts a wide range of tasks, including physical patterning processes, and cell-cell interactions [8,9]. In protection, thermal insulation, camouflage, dispersion of addition, hair follicles and shafts are of significant cos- sweat and sebum, sensory and tactile functions, and so- metic relevance. The follicle provides the source for hair cial interactions [4]. In human society, hair is of enor- production and, thus, eventually determining appearance mous, psychosocial importance, and many human dis- by affecting the hair shaft’s structure and shape. Hair eases are associated with abnormalities in hair follicle features are not only affected by the follicle’s capacity to morphogenesis, cycling, and structure. give rise to a normal shaft but also by the so-called hair A hair grows from the papilla and with the exception growth cycle which controls the periodic growth and of that point of generation is made up of dead, cornified shedding of hair. cells. It consists of a shaft that projects above the skin, Human hair is one of most keratinous fibres. There are *Corresponding author. various fibre shapes in human hair and it is commonly Copyright © 2013 SciRes. JCDSA Mutations with Hair Shape Phenotypes Abnormalities—The Morphogenetic Waves and Related Diseases 27 accepted that the curliness of hair fibres is roughly clas- wavy body hair in Re/+ and body hair loss in Re/Re rats sified by their ethnic origin in the three major ethnic after the first molt. The homozygote exhibits more waved groups: African hair which has a strong curl shape, Cau- pelage and smaller body size and histological analysis of casian hair which has a moderately waved shape, and 1-month-old mice revealed bent hair follicles and fragile Asian hair which is apt to have a comparatively straight hair shafts, vibrissae of the homozygote are more shape [10]. The corresponding difference in the internal strongly curled than those in the heterozygote [17,18]. nanostructure, however, still remains unrevealed. Recently, genome-wide single-nucleotide polymor- The structured pattern of hair is determined by their phism (SNP) association studies led to candidate gene length, width, and shape. Whereas the prototype hair is screening for the curly/wavy coat of the portuguese water straight, hair can adopt different shapes owing to bend- dog. A SNP in keratin-71 (KRT71) was shown to cause a ing. In principle, bending could be achieved by diverse nonsynonymous mutation in exon 2, having been re- means. Differences in cell proliferation on opposite sides cently identified in curly hair in dogs [19]. In cat, a com- of the hair follicle would inevitably give rise to hair cur- plex sequence alteration of the KRT 71 gene, also caus- vature [11]. Understanding the factors that contribute to ing a splice variation, was identified in the Devon Rex the curly morphology of human hair is important for an- breed with curly coats [20]. In cattle, an autosomal re- thropological and physiological studies. According to a cessive form has been described in Hereford cattle, an recent report, hair curling in man is a consequence of 8-bp deletion mutation occurring in exon 1 causes an different proliferation rates within the hair follicle that early truncated KRT71 protein resulting in a curly-hair appear to be reflected by the shape of the follicle [12,13]. coat [21]. More gene mutations affecting the morphoge- This correlation is reminiscent of the potential link be- netic waves are showed in the Table 1. tween follicle and hair size. Curliness has commonly been assessed using words 3. Hair Curliness-Related Inherited Diseases such as straight, wavy, curly and frizzy, a variety of at- tributes of subjective nature with no clear definition and 3.1. Pseudofolliculitis Barbae (PFB) limits [14]. Curly hair is very common character of hair Pseudofolliculitis barbae, a common human hair disorder, phenotypes of human, which is caused by many reasons. showing a chronic, irritating, and potentially disfiguring Most congenital curl occurs as the result of genetic fac- condition that develops as a result of attempts to elimi- tors and some are closely related with genetic diseases. nate hair from the beard area, usually by shaving [56]. Genetic analyses of common diseases in humans have re- The disease is, however, not gender-specific, nor re- vealed that gene mutations are involved in diseases. Ge- stricted to the face, but can occur in any hairy skin region nome sequencing projects of various mammalian species upon regular shaving or other means of hair removal [57]. followed by comparative genome analyses have revealed Compared to Caucasian males, black males are distinctly that a large number of genes are shared among species. more susceptible to developing PFB due to their genetic Thus, it is thought that mutations found in model animals predisposition for strongly curved hairs and the study and animals carrying such mutations are of large signifi- showed that incidence rate of the disorder can affect up cance in studying hair growth regulation and the rela- to 1 out of every 5 Caucasian individuals while it occurs tionship with some hereditary diseases. much more commonly in black persons [58]. The muta- tion analysis of K75 and the IRS keratins in a three-gen- 2. The Curly Hair-Specific Genes eration Caucasian family whose male members suffered Several genetic alterations with different follicular local- from relatively severe PFB symptoms revealed that af- izations of the primary aberration give rise to curly or fected males exhibited a heterozygous point mutation in wavy hair and curly pelage is an easily recognized trans- the KRT75 gene. The mutation was also present in a fe- species coat anomaly, moreover, several detailed studies male member of the family, however, this individual did in various mammalian species. In mice, Caracul (Ca) not shave nor remove hairs by other means, and she was mice, a dominant mutation mapped to mouse chromo- free of symptoms. Clinical features include the appear- some 15 and missense point to a single amino acid ex- ance of inflammatory papules and pustules. Molecular change at the beginning of the a-helical rod domain of analysis in a family study and a large-scale investigation Krt71, a few amino acids apart from four identified Ca of randomly sampled PFB-affected and -unaffected indi- alleles possess curly hair and vibrissae after birth [15]. viduals showed that an unusual single-nucleotide poly- two novel krt 71rco12 and rco13 mutant mice, displaying a morphism, which gives rise to a disruptive Ala12Thr wavy pelage and curly vibrissae, have been identified as substitution in the 1A a-helical segment of the compan- missense point mutations in the first exon of the krt ion layer-specific keratin K6hf of the hair follicle, is par- 71gene [16]. In rat, the autosomal dominant Rex (Re) tially responsible for the phenotypic expression and mutation in the Krt71 gene, on chromosome 7, causes represents an additional genetic risk factor for PFB [59].
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