User:Mona Ibsa/Keratin disease

A keratin disease is a genetic disorder of one of the keratin genes.^{[citation needed]} An example is monilethrix. The first to be identified was epidermolysis bullosa simplex.

Pathology

Examples of keratin disease include:

Name	Skin/hair	Keratin
Epidermolysis bullosa simplex	skin	KRT5, KRT14
Epidermolytic hyperkeratosis	skin	KRT1, KRT10
Ichthyosis bullosa of Siemens	skin	KRT2A
Palmoplantar keratoderma	skin	KRT1, KRT9, KRT16
Pachyonychia congenita	skin	KRT6A, KRT6B, KRT16, KRT17
White sponge nevus	skin	KRT4, KRT13
Steatocystoma multiplex	skin	KRT17
Monilethrix	hair	KRT81, KRT83, KRT86
Meesman juvenile epithelial corneal dystrophy	cornea	KRT3, KRT12
Familial cirrhosis	liver	KRT8, KRT18

See also[edit]

• List of cutaneous conditions caused by mutations in keratins

Human keratins structural support

Figure 1: Keratinocytes, basal cells, and melanocytes in the epidermis as seen in a micrograph.

As one of the cytoskeletal proteins in the cell’s cytoplasm, keratin play an essential role with 54 gene types. A total of 28 type I keratin genes (17 epithelial keratins and 11 hair keratins) and 26 type II keratin genes (20 epithelial keratins and 6 hair keratins) exists with 26 (50%) being present in the hair follicle. Among the keratin genes in the human genome, there are two distinct clusters: 17q21.2 (type I keratins, except K18) and 12q13.13 (type II keratins, including K18). In figure1, it shows how the domains of human keratin genes for type I and type II are expressed in different colours and with different characteristics on chromosomes 17q21.2 and 12q13.13.

Figure 2: (a) Keratin genes of type I. (b) Type II keratin genes are highlighted in red. The blue genes express epithelium (skin) keratins; the green genes express particular epithelial hair follicle keratins; and the black genes express hair keratin genes, which are pseudogenes. 1 KRT18 is a gene of type I.

Keratin abnormalities

Disease pathology may also be affected by the other gene modifiers, which are poorly understood. It is becoming increasingly evident that keratin diseases are highly heterogeneous in terms of their phenotypic variations. A mutation in the same keratin gene can differ in severity based on its location in the protein.

EBS (epidermolysis bullosa simplex) disorder

The factors of the keratin intermediate filament heteropolymer can impair the mechanical steadiness of these epithelial cells. There are at least sixteen one-of-a-kind sorts of epidermolysis bullosa (EB), an ailment in which the pores and skin develops blisters after solely moderate irritation.

File:Nihms-266905-f0003.jpg

The clinical features of epidermolysis bullosa simplex (EBS) and epidermolytic ichthyosis (EI) are as follows: (a) A child's hand displaying the severe generalized Dowling-Meara form of EBS, characterized by numerous herpetiform blisters that heal without forming scars. (b) An adult with severe EBS-DM who experiences painful plantar callosities on their feet. (c) Epidermolytic ichthyosis patients showing pronounced massive hyperkeratosis on their lower back. (d) Diffuse hyperkeratosis visible on the hands and flexures against an erythromatous background in EI cases.

EI (epidermolytic ichthyosis) disorder

Epidermolytic ichthyosis, previously known as bullous congenital ichthyosiform erythroderma (BCIE) or Epidermolytic hyperkeratosis (EHK), is a rare skin fragility disease that is typically inherited in an autosomal dominant manner and falls under the category of congenital ichthyosis. This condition arises due to mutations in the K1 and K10 genes which are responsible for encoding epidermal suprabasal keratin 1 or 10 expressed in keratinocytes of the suprabasal layers of the epidermis. The onset of symptoms may occur at birth or shortly after, with scaling, reddening, and severe blistering of the skin being common indications. Symptoms can appear during different age ranges depending on various factors such as genetics. Although blister formation tends to decrease over time, it may still happen upon skin trauma or during warmer months. Additionally, there might be associated itching and foul odors accompanied by increased susceptibility to infections due to impaired epithelial barrier function leading to electrolyte imbalances and sepsis risk among neonates with EI. The cutaneous pathology resulting from defective expression of abnormal K1 or K10 proteins causes more superficial but widespread blistering than EBS and increased proliferation leading to scaly lesions resembling fish scales which vary according to location along keratin polypeptides where mutations occurred alongside altered gene expression levels determining clinical presentation patterns in this disorder too.

Hair disorders

Hair disorders are problems in humans that include hair loss/growth, structural flaws in the hair strands with excessive breakage, and an unattractive physical appearance (ex. weak, elasticity, unshiny hair). Just 7 functional keratins are associated to human genetic diseases in type I keratins. The functional type I keratins include K81, K83, K86, K85, K75, K71, and K74. The mutation of K81, K83, or K86 is the cause of the diseases Monilethrix. Monilethrix is a condition in which the hair breaks readily, particularly over areas of friction, such as the occipital area. All three type I keratin genes are mostly expressed in the keratinizing zone of the hair shaft's cortex. This disrupts the production of the keratin intermediate filaments in the cortex of the hair shaft. Another hair disorder is Peptidyl arginine deiminase, type III, an essential hair protein (PADI3). PADI3 is significantly present in the hair disease CCCA, where it warrants additional genetic analysis and characterization. The woolly hair is caused by an autosomal dominant mutation in the inner root sheath keratins, K71 or K74. The K75 mutation is expressed in the hair follicle's outer layers. The combination of genetic predisposition and the environmental stimulus of shaving is a substantial genetic risk factor for pseudofolliculitis barbae.

Nail disorder

Pachyonychia congenita (PC) is a rare autosomal dominant genetic disorder affecting the skin and nails, which results from nail mutations in K6/K16/K17 cells. It is characterized by hypertrophic nail dystrophy and exists in two forms. Symptoms generally appear at birth or early on, with no specific racial or ethnic predilection between both sexes.

The condition stems from mutations that affect keratins - proteins vital to cell structure - classified into five types based on affected gene location. Although symptoms may vary depending on the type, thickened nails and calluses are observed in almost all cases.

PC has two subtypes: pachyonychia congenita type I (PC-I) and pachyonychia congenita type II (PC-II). In PC-I patients, the genes responsible for encoding stress-responsive K6a and wound-healing-induced K16 have been found mutated; their distribution across epithelial tissues such as nail bed/fold matches well with the phenotype of epithelial fragility seen among these individuals' population group.

On the other hand, those suffering from PC-II exhibit mild palmoplantar keratoderma alongside hyperkeratosis-induced pilosebaceous cysts which develop after puberty typically resulting in hair abnormalities like twisted hair but without complete penetrance often accompanied by natal teeth.