Canine coat pigmentation genetics: a review.

Our understanding of canine coat colour genetics and the associated health implications is developing rapidly. To date, there are 15 genes with known roles in canine coat colour phenotypes. Many coat phenotypes result from complex and/or epistatic genetic interactions among variants within and between loci, some of which remain unidentified. Some genes involved in canine pigmentation have been linked to aural, visual and neurological impairments. Consequently, coat pigmentation in the domestic dog retains considerable ethical and economic interest. In this paper we discuss coat colour phenotypes in the domestic dog, the genes and variants responsible for these phenotypes and any proven coat colour-associated health effects.

Role of Amine Neurotransmitters and Their Receptors in Skin Pigmentation: Therapeutic Implication.

Skin pigmentation can occur due to increased melanin, including melanocyte proliferation, melanin biosynthesis, or melanocyte migration. There are many factors that influence the melanin production process, but the role of neurotransmitters in this process is still unclear. We found that histamine and serotonin influence the different stages of melanogenesis and melanogenesis, which increase melanogenesis. Since then, several related papers have been published, and from these papers, it has been recognised that the role of neurotransmitters in skin-pigment-related diseases needs to be summarised. By introducing the role of neurotransmitters in the regulation of various pigment disorders, including vitiligo and melasma, through this review, many researchers can be expected to try to apply neurotransmitter-related agonists and antagonists as treatments for skin pigment disorders.

Cyclic adenosine monophosphate (cAMP) signaling in melanocyte pigmentation and melanomagenesis.

The second messenger cyclic adenosine monophosphate (cAMP) regulates numerous functions in both benign melanocytes and melanoma cells. cAMP is generated from two distinct sources, transmembrane and soluble adenylyl cyclases (tmAC and sAC, respectively), and is degraded by a family of proteins called phosphodiesterases (PDEs). cAMP signaling can be regulated in many different ways and can lead to varied effects in melanocytes. It was recently revealed that distinct cAMP signaling pathways regulate pigmentation by either altering pigment gene expression or the pH of melanosomes. In the context of melanoma, many studies report seemingly contradictory roles for cAMP in tumorigenesis. For example, cAMP signaling has been implicated in both cancer promotion and suppression, as well as both therapy resistance and sensitization. This conundrum in the field may be explained by the fact that cAMP signals in discrete microdomains and each microdomain can mediate differential cellular functions. Here, we review the role of cAMP signaling microdomains in benign melanocyte biology, focusing on pigmentation, and in melanomagenesis.

Melanin-concentrating hormone like and somatolactin. A teleost-specific hypothalamic-hypophyseal axis system linking physiological and morphological pigmentation.

Plastic adaptation to match the skin colour to the surrounding is key to survival. Two biological responses in skin colour are associated with background adaptation. A fast "physiological response" that aggregates/disperses the pigment organelles of skin chromatophores, and a slow "morphological response" that alters the type and/or density of pigment cells in the skin. Both responses are linked by unknown mechanisms. In this review, we discuss the role in skin colour regulation of two molecules that form part of a hypothalamic-hypophyseal pathway unique to teleosts, melanin-concentrating hormone "like" (MCHL) (previously known as MCH), and somatolactin. MCHL neurons project to the neurohypophysis and to the pars intermedia pituitary, where they interact with somatolactin-expressing cells. With a white background MCHL is released into the circulation to induce rapid melanosome aggregation and skin lightening. Somatolactin is also a fish-specific peptide whose expression and secretion are altered in organisms adapted chronically to white/black backgrounds, and that regulates morphological pigmentation. We discuss the evidence for a model whereby in teleosts, MCHL and somatolactin provide the previously unknown link between physiological and morphological pigmentation.

Time gap between the onset and diagnosis in Werner syndrome: a nationwide survey and the 2020 registry in Japan.

Patients with Werner syndrome present with diverse signs of aging that begin in adolescence. A Japanese nationwide survey was conducted to establish a registry that could clarify the disease profile of patients with Werner syndrome. The questionnaires were sent to 7888 doctors. The survey identified 116 patients diagnosed with Werner syndrome based on the diagnosis criteria. Forty patients were enrolled in the registry. Data on clinical symptoms, treatment information, and laboratory examination from patients who provided informed consent were collected. The data at enrollment were analyzed. The patients' average age at enrollment was 50.1±7.5 years. The mean onset age was 26.1±9.5 years, but the mean age at diagnosis was 42.5±8.6 years. Average height and weight of the study patients were lower than those of Japanese individuals. Almost all patients experienced hair change and cataracts. More than 60% of patients presented with glycolipid abnormalities. Overall, 15% of patients had a history of foot amputation. Approximately 30% of the patients' parents had a consanguineous marriage. The average grip strength, walking speed, and skeletal muscle mass index met the diagnostic criteria for sarcopenia. The registry revealed that there are opportunities for early diagnosis and intervention; therefore, sensitization about the disease is needed.

Presentación clínica de pigmentación melánica fisiológica / Clinical presentation of physiologic melanin pigmentation

Las pigmentaciones de la cavidad oral son comunes, éstas pueden representar diversas entidades clínicas, desde cambios fisiológicos hasta cambios malignos. Las pigmentaciones en la encía se conocen como pigmentaciones melánicas o melanosis gingival; en la encía se observan como tinciones oscuras ocasionadas por la acumulación de melanina en la zona. Éstas se consideran comunes, pueden representar variación normal en la pigmentación de melanina de la mucosa oral, hasta representar procesos malignos. En general, las personas de piel más oscura presentan frecuentemente mayor pigmentación de melanina oral que las personas de piel clara. Las variaciones en la pigmentación fisiológica oral están determinadas genéticamente a menos que estén asociadas con alguna enfermedad subyacente (AU)

Pigmentation of the oral cavity is common, it can represent diverse clinical entities, from physiological changes to malignant changes. Gum pigmentations are known as melanic pigmentations or gingival melanosis, and are observed as dark stains caused by the accumulation of melanin in the localized area. These are considered common, they can represent normal variation in melanin pigmentation of the oral mucosa, or malignant processes. In general, people with darker skin often exhibit greater pigmentation of oral melanin than people with fair skin. Variations in oral physiological pigmentation are genetically determined unless they are associated with some underlying disease (AU)

Topical treatment strategies to manipulate human skin pigmentation.

Skin pigmentation is a result of melanin produced by melanocytes in the epidermis. Melanocyte activity, along with the type and distribution of melanins, is the main driver for diversity of skin pigmentation. Dark melanin acts to protect against the deleterious effects of ultraviolet (UV) radiation, including photo-aging and skin cancer formation. In turn, UV radiation activates skin melanocytes to induce further pigmentation (i.e., "tanning pathway"). The well-characterized MSH/MC1R-cAMP-MITF pathway regulates UV-induced melanization. Pharmacologic activation of this pathway ("sunless tanning") represents a potential strategy for skin cancer prevention, particularly in those with light skin or the "red hair" phenotype who tan poorly after UV exposure due to MC1R inactivating polymorphisms. Skin hyperpigmentation can also occur as a result of inflammatory processes and dermatological disorders such as melasma. While primarily of cosmetic concern, these conditions can dramatically impact quality of life of affected patients. Several topical agents are utilized to treat skin pigmentation disorders. Here, we review melanogenesis induced by UV exposure and the agents that target this pathway.

Premature cell senescence in human skin: Dual face in chronic acquired pigmentary disorders.

Although senescence was originally described as an in vitro acquired cellular characteristic, it was recently recognized that senescence is physiologically and pathologically involved in aging and age-related diseases in vivo. The definition of cellular senescence has expanded to include the growth arrest caused by various cellular stresses, including DNA damage, inadequate mitochondria function, activated oncogene or tumor suppressor genes and oxidative stress. While senescence in normal aging involves various tissues over time and contributes to a decline in tissue function even with healthy aging, disease-induced premature senescence may be restricted to one or a few organs triggering a prolonged and more intense rate of accumulation of senescent cells than in normal aging. Organ-specific high senescence rate could lead to chronic diseases, especially in post-mitotic rich tissue. Recently, two opposite acquired pathological conditions related to skin pigmentation were described to be associated with premature senescence: vitiligo and melasma. In both cases, it was demonstrated that pathological dysfunctions are not restricted to melanocytes, the cell type responsible for melanin production and transport to surrounding keratinocytes. Similar to physiological melanogenesis, dermal and epidermal cells contribute directly and indirectly to deregulate skin pigmentation as a result of complex intercellular communication. Thus, despite senescence usually being reported as a uniform phenotype sharing the expression of characteristic markers, skin senescence involving mainly the dermal compartment and its paracrine function could be associated with the disappearance of melanocytes in vitiligo lesions and with the exacerbated activity of melanocytes in the hyperpigmentation spots of melasma. This suggests that the difference may arise in melanocyte intrinsic differences and/or in highly defined microenvironment peculiarities poorly explored at the current state of the art. A similar dualistic phenotype has been attributed to intratumoral stromal cells as cancer-associated fibroblasts presenting a senescent-like phenotype which influence the behavior of neoplastic cells in either a tumor-promoting or tumor-inhibiting manner. Here, we present a framework dissecting senescent-related molecular alterations shared by vitiligo and melasma patients and we also discuss disease-specific differences representing new challenges for treatment.

The Genetics of Human Skin and Hair Pigmentation.

Human skin and hair color are visible traits that can vary dramatically within and across ethnic populations. The genetic makeup of these traits-including polymorphisms in the enzymes and signaling proteins involved in melanogenesis, and the vital role of ion transport mechanisms operating during the maturation and distribution of the melanosome-has provided new insights into the regulation of pigmentation. A large number of novel loci involved in the process have been recently discovered through four large-scale genome-wide association studies in Europeans, two large genetic studies of skin color in Africans, one study in Latin Americans, and functional testing in animal models. The responsible polymorphisms within these pigmentation genes appear at different population frequencies, can be used as ancestry-informative markers, and provide insight into the evolutionary selective forces that have acted to create this human diversity.

Pigmentation abnormalities in nucleotide excision repair disorders: Evidence and hypotheses.

Skin pigmentation abnormalities are manifested in several disorders associated with deficient DNA repair mechanisms such as nucleotide excision repair (NER) and double-strand break (DSB) diseases, a topic that has not received much attention up to now. Hereditary disorders associated with defective DNA repair are valuable models for understanding mechanisms that lead to hypo- and hyperpigmentation. Owing to the UV-associated nature of abnormal pigmentary manifestations, the outcome of the activated DNA damage response (DDR) network could be the effector signal for alterations in pigmentation, ultimately manifesting as pigmentary abnormalities in repair-deficient disorders. In this review, the role of the DDR network in the manifestation of pigmentary abnormalities in NER and DSB disorders is discussed with a special emphasis on NER disorders.

A randomized study to evaluate the efficacy and effectiveness of two sunscreen formulations on Indian skin types IV and V with pigmentation irregularities.

BACKGROUND: Regular exposure to ultraviolet rays is high in India, where most Indians present Fitzpatrick skin phototypes IV and V. AIMS: To evaluate the efficacy and compare the effectiveness of two sunscreen products on Indian skin types IV and V with pigmentation irregularities. METHODS: A randomized, uncontrolled and investigator-blinded, single-center study enrolled adult men and women (18-45 years) with Fitzpatrick skin phototypes IV (28° < individual typological angle <10°) and V (10° < individual typological angle < -30°) with pigmentary abnormalities seen on the face in adults (actinic lentigines and postinflammatory hyperpigmentation), who did not use sunscreens. Participants were randomized (1:1) to either of the two marketed sunscreen products, Product A (sun protection factor 50 PA+++) or Product B (sun protection factor 19 PA+++), applied twice daily before sun exposure for ≥2 h. Primary objectives aimed at assessing possible improvement in hyperpigmented spots and overall skin appearance after 12 weeks of use. Evaluation of skin radiance and skin color was done by means of L'Oréal color chart and colorimetric measurements (Chromameter®). RESULTS: Among the 230 enrolled participants, 216 (93.91%) completed the study. The clinical assessment of the density of pigmented spots and skin radiance showed significant (P < 0.001) improvement in both groups during all visits. The qualitative (participant perception) and quantitative (Chromameter®) data indicated improvement in pigmentation from Week 0 to Week 12. Both products were well-tolerated. LIMITATIONS: The study was conducted over a rather short period of time (12 weeks) at a single location. CONCLUSIONS: This is the first study conducted on Indian skin phototypes IV and V under real-life conditions. It demonstrated the effect of regular sunscreen usage in the prevention of certain signs of skin photoaging such as increased pigmentation or pigmentary abnormalities, thus providing support and assistance to clinicians in suggesting the use of efficient sun-screening products to patients.

Terminal osseous dysplasia with pigmentary defects (TODPD) in a Turkish girl with new skin findings.

Terminal osseous dysplasia with pigmentary defects (TODPD; MIM #300244) is an extremely rare, X-linked dominant, in utero male-lethal disease, characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin, and recurrent digital fibromatosis of childhood. Delayed/abnormal ossification of bones of the hands and feet, joint contractures, and dysmorphic facial features may accompany. A single recurrent mutation (c.5217 G>A) of the FLNA gene which causes cryptic splicing was identified as the cause of the disease. We here present the first TODPD case from Turkey with full-blown phenotype who exhibit unique additional findings, hypopigmented patch on the lower extremity following Blaschko's lines and smooth muscle hamartoma of the scalp in review of all the previously reported TODPD cases.

The physiology of melanin deposition in health and disease.

Eumelanin is the major pigment responsible for human skin color. This black/brown pigment is localized in membrane-bound organelles (melanosomes) found in specialized cells (melanocytes) in the basal layer of the epidermis. This review highlights the steps involved in melanogenesis in the epidermis and the disorders in skin pigmentation that occur when specific steps critical for this process are defective. Melanosomes, which contain tyrosinase, a major enzyme involved in melanin synthesis, develop through a series of steps in the melanocyte. They are donated from the melanocyte dendrites to the surrounding keratinocytes in the epidermis. In the keratinocytes, the melanosomes are found singly or packaged into groups, and as the keratinocytes move upward in the epidermis, the melanosomes start to degrade. This sequence of events is critical for melanin pigmentation in the skin and can be influenced by genetic, hormonal, and environmental factors, which all play a role in levels of melanization of the epidermis. The effects these factors have on skin pigmentation can be due to different underlying mechanisms involved in the melanization process leading to either hypo- or hyperpigmentary disorders. These disorders highlight the importance of mechanistic studies on the specific steps involved in the melanization process.

PDT and BF-200 ALA: The therapy option for the treatment of Poikiloderma of Civatte.

Poikiloderma is a chronic skin condition affecting middle-age men and women that comprises cutaneous atrophy, telangiectasias, and changes in the pigmentation of the skin usually of mottled appearance (both hyper- and hypopigmentation). There is no specific medical treatment for Poikiloderma of Civatte (PC), but the use of photoprotector/sunscreen + SPF 50 to avoid prolonged sun exposure is highly recommended in these patients. Some authors recommend the use of topical corticoids in early stages; however, the results have not been satisfactory. Multiple topical (retinoids, dimethyl sulfoxide, or calcineurin inhibitors), systemic (cyclophosphamide), and physical (dermabrasion, phototherapy, and fractional photothermolysis) treatments have been described with unequal and inconsistent responses or unsatisfactory. This report underlies the combination of BF-200 ALA and photodynamic therapy (PDT) with positive results at the clinical level: significant improvement of pigmentary changes and telangiectasias after two PDT sessions.

Evaluation of the anterior chamber angle in pseudoexfoliation syndrome.

BACKGROUND: Pseudoexfoliation syndrome (PEX) is the most frequently identifiable cause of secondary open-angle glaucoma, known as pseudoexfoliation glaucoma. The exact pathophysiology and etiology of PEX and associated glaucoma remains obscure. OBJECTIVES: The purpose of this study was to determine the differences in the morphology of the anterior chamber angle in people with pseudoexfoliation syndrome and pseudoexfoliation glaucoma compared to a control group. We also evaluated the correlation between intraocular pressure (IOP) and pigmentation of the angle with the amount of exfoliated material in the anterior segment. MATERIAL AND METHODS: The study group was composed of 155 eyes from 103 patients aged between 43 and 86 years. Each patient underwent a complete ophthalmological examination. RESULTS: Some difference was found in intraocular pressure between the PEX group and the control group and between the pseudoexfoliation glaucoma group and the control group, but no significant difference was found between the 2 study groups. There was a significant difference in the incidence of some degree of pigmentation in the anterior chamber angle and no difference in the widths of the angle between each group. A significant positive relationship was observed between intraocular pressure and the degree of pigmentation of the anterior chamber angle in both the PEX group and the pseudoexfoliation glaucoma group. CONCLUSIONS: The results of this study indicate that the amount of pigmentation and exfoliation material in the anterior segment significantly correlates with the level of IOP and possibly with the degree of trabecular dysfunction. It seems that for clear identification of PEX and pseudoexfoliation glaucoma factors, clinical assessment appears to be insufficient.

Forceps trauma in a newborn presenting as iris heterochromia.

Birth-associated ocular trauma is common and often minor, including subconjunctival and retinal haemorrhage and eyelid edema. Significant ocular trauma during birth, usually associated with forceps-assisted delivery, is rarer and can include Descemet's membrane rupture, lid lacerations, hyphema, Purtcher retinopathy, facial nerve palsy, corneal edema, and corneal laceration. We report the first case of ocular birth trauma from forceps presenting as isolated iris heterochromia and a pseudo rubeosis iridis, which completely resolved by 1 month of age with no known adverse ocular sequelae.

Ito syndrome.

Children with Ito syndrome have the common feature of unusual pigmentation in a characteristic swirling pattern located around the trunk, and as line-like patterns down the legs and arms.