BACKGROUND: Piebaldism is a rare autosomal dominant disorder characterized by congenital white forelock and depigmented patches, which is most commonly caused by deleterious variants in the KIT gene.
METHODS: Four KIT variants were identified in a piebaldism case series by whole-exome sequencing. Functional experiments, including in vitro minigene reporter assay and enzyme-linked immunosorbent assay, were carried out to elucidate the pathogenicity of the variants. The genotype-phenotype correlation was summarized through extensive literature reviewing.
RESULTS: All the four cases had severe piebaldism presented with typical white forelock and diffuse depigmentation on the ventral trunk and limbs. Four germline variants at the tyrosine kinase (TK) domains of the KIT gene were identified: two novel variants c.1990+1G>A (p.Pro627_Gly664delinsArg) and c.2716T>C (p.Cys906Arg), and two known variants c.1879+1G>A (p.Gly592_Pro627delinsAla) and c.1747G>A (p.Glu583Lys). Both splicing variants caused exon skipping and inframe deletions in the TK1 domain. The missense variants resided at the TK1 and TK2 domains respectively impairing PI3K/AKT and MAPK/ERK signaling pathways, the downstream of KIT. All severe cases were associated with variants in the TK domains, eliciting a major dominant-negative mechanism of the disease.
CONCLUSIONS: Our data expand the mutation spectrum of KIT, emphasized by a dominant-negative effect of variants in the critical TK domains in severe cases. We also share the experience of prenatal diagnosis and informed reproductive choices for the affected families.

Pruritus, rash, and various other forms of dermatotoxicity are the most frequent adverse events among patients with cancer receiving targeted molecular therapy and immunotherapy. Immune checkpoint inhibitors, macrophage-targeting agents, and epidermal growth factor receptor/MEK inhibitors not only exert antitumor effects but also interfere with molecular pathways essential for skin immune homeostasis. Studying cancer therapy-induced dermatotoxicity helps us identify molecular mechanisms governing skin immunity and deepen our understanding of human biology. This review summarizes new mechanistic insights emerging from the analysis of cutaneous adverse events and discusses knowledge gaps that remain to be closed by future research.

UNASSIGNED: In addition to sensorineural hearing loss, Waardenburg Syndrome (WS) may present with variable pigmentation of skin and choroid, which may simulate other life-threating conditions (e.g. melanoma).
UNASSIGNED: Two siblings ostensibly presented with unilateral choroidal pigmentary abnormalities concerning for choroidal tumour. Serial ophthalmic examination documented no lesion growth (base or height) whilst the apparent syndromic features (i.e. iris hypochromia, profound sensorineural hearing loss, SNHL), family history (autosomal dominant inheritance) and positive genetic testing (pathogenic MITF variant) led to a revised diagnosis of Waardenburg Syndrome type 2A.
UNASSIGNED: Sectoral preservation of choroidal pigmentation in WS is rarely associated with choroidal malignancy. Awareness of syndromic features (e.g. SNHL) and access to genetic testing may facilitate early accurate diagnosis (i.e. allay concern for malignancy), enable treatment of modifiable features (e.g. SNHL) and identify other affected relatives.

Zebrafish larvae exposed to chemoconvulsants show behavioral seizures and electrographic abnormalities similar to the other mammalian models, making it a potential tool in epilepsy research. During the embryonic stage, zebrafish remains transparent which enables real-time developmental detection and in-situ gene/protein expression. However, pigmentation during the larval stage restricts transparency. Phenylthiourea (1-phenyl-2-thiourea; PTU) is a commonly used pigmentation blocker that maintains larval transparency. It is widely used along with chemoconvulsants to study in situ expressions in epileptic larvae, however, its effect on seizures largely remains unknown. Therefore, in the present study, the effect of PTU-mediated depigmentation was studied on pentylenetetrazol (PTZ)-induced seizures in zebrafish larvae. After spawning, the fish embryos were subjected to standard depigmentation protocol using 0.13 mM PTU. At 7-days post fertilization seizures were induced using 8 mM PTZ. PTU exposure significantly reduced PTZ-mediated hyperactive responses indicated by decreased distance travelled and swimming velocity of the larvae. Furthermore, PTU-exposed depigmented larvae also showed an increase in the latency to the onset of PTZ-mediated clonic-like seizures. The results concluded that PTU depigmentation protocol reduces the seizurogenic response of PTZ, hence its usage for imaging zebrafish larvae must be carefully monitored to avoid erroneous results.

The most common aesthetic issue that affects people\'s smiles is gingival pigmentation, especially in those with high smile lines. This pigmented gingiva is thought to be naturally occurring melanin pigments that add to the gingiva\'s endogenous pigmentation. The goal of plastic periodontal surgery known as \"gingival depigmentation\" is to lighten the dark gingiva by scraping off the gingival epithelium. Gingival depigmentation has been performed with a variety of techniques, including bur abrasion, scraping, partial thickness flap, cryotherapy, electrocautery, and laser. The present case comprised a split-mouth design in which depigmentation using an electrosurgical unit and soft tissue trimming bur was used for the maxillary sections, and evaluated the difference in pain felt by the patient and healing of the surgical site between the sites treated with the electrosurgical unit and bur abrasion method. A visual analog scale (VAS) was used to quantify pain felt by the patient on the seventh day, whereas healing was assessed on the seventh day and at a one-month interval visually. The results of this study showed that the electrocautery-treated site showed better results in terms of pain experienced by the patient and also with the surgical site healing.

UNASSIGNED: Programmed death ligand 1 (PD-L1) score is an important companion diagnosis to predict the response to immunotherapy. Immunohistochemistry can accurately assess the expression of PD-L1 in routine paraffin-embedded tissue. However, whether decalcified or depigmented tissue is still accurate and can be used as a companion diagnosis is controversial. This study attempts to resolve this controversy by analyzing the effects of decalcification and depigmentation at different times on PD-L1 expression.
UNASSIGNED: Placental tissues were selected for tissue microarray, decalcification was performed according to time gradients of 6, 12, 24, 36, and 48 h, and depigmentation was performed according to time gradients of 1, 5, 15, 30, and 60 min. The intensity of PD-L1 expression at different time points was observed and quantified. Ten PD-L1-positive esophageal squamous carcinoma samples were selected for decalcification treatment, and the PD-L1. Combined Positive Score (CPS), Tumor Proportion Score (TPS) and Immunocyte Proportion Score (IPS) and the positivity rates were compared before and after decalcification.
UNASSIGNED: After the placenta was decalcified, the intensity of PD-L1 positivity diminished, and the average optical density (AOD) value decreased with the prolongation of decalcification time and decreased significantly (P<0.05) at 24 h compared with the control group, and significantly (P<0.01) at 36 and 48 h compared with the control group. The intensity of PD-L1 positivity was weakened considerably after the treatment with potassium permanganate depigmentation. In addition, the AOD value decreased significantly (P<0.01) after the depigmentation time reached 5 min compared with the control group. Ten cases of PD-L1 positive esophageal squamous carcinoma were treated with 24 h decalcification, although the PD-L1 score decreased to a certain degree (P>0.05), and the positivity rate could reach 90%. After 36 h treatment, PD-L1 scores decreased, the CPS and IPS scores decreased significantly (P<0.05), and the positive rate was only 50%.
UNASSIGNED: Potassium permanganate depigmentation significantly reduces PD-L1 expression, even for a shorter time, affecting the accuracy of the results. The accuracy of PD-L1 remained high within 24 h decalcification. The above results have certain reference value for clinical selection of immunotherapy.

Oral neomycin administration impacts the gut microbiome and delays vitiligo development in mice, and topical antibiotics may likewise allow the microbiome to preserve skin health and delay depigmentation. Here, we examined the effects of 6-week topical antibiotic treatment on vitiligo-prone pmel-1 mice. Bacitracin, Neosporin, or Vaseline were applied to one denuded flank, while the contralateral flank was treated with Vaseline in all mice. Ventral depigmentation was quantified weekly. We found that topical Neosporin treatment significantly reduced depigmentation and exhibited effects beyond the treated area, while Bacitracin ointment had no effect. Stool samples collected from four representative mice/group during treatment revealed that Neosporin treatment aligned with reduced abundance of the Alistipes genus in the gut, while relevant changes to the skin microbiome at end point were less apparent. Either antibiotic treatment led to reduced expression of MR1, potentially limiting mucosal-associated invariant T-cell activation, while Neosporin-treated skin selectively revealed significantly reduced CD8+ T-cell abundance. The latter finding aligned with reduced expression of multiple inflammatory markers and markedly increased regulatory T-cell density. Our studies on favorable skin and oral antibiotic treatment share the neomycin compound, and in either case, microbial changes were most apparent in stool samples. Taken together, neomycin-containing antibiotic applications can mediate skin Treg infiltration to limit vitiligo development. Our study highlights the therapeutic potential of short-term antibiotic applications to limit depigmentation vitiligo.

UNASSIGNED: Platelet-rich fibrin (PRF) accelerates wound healing by promoting faster cicatricial tissue remodeling and excellent neovascularization. Hyaluronic acid (HA) being biocompatible, anti-inflammatory, and proangiogenic leads to improvement in the rate of wound healing.
UNASSIGNED: The aim of this study was to compare the effect of PRF membrane and 0.2% HA gel on wounds after gingival depigmentation surgery.
UNASSIGNED: This study was carried out on 30 systemically healthy individuals recruited from the pool of patients who visited the department of periodontology. After depigmentation procedure in every patient, the sites were divided into three even groups. Group A received PRF membrane and periodontal dressing, Group B received 0.2% HA gel application and periodontal dressing, and Group C served as a control group in which only periodontal dressing was placed. The individuals were evaluated for the healing index (HI) and Numerical Rating Scale (NRS) on the 3rd and 5th day. Epithelialization test (ET) was performed on the 5th day. Gingival biotype was reassessed and compared to preoperative value after 3 months. The clinical trial was expressed in terms of mean and standard deviation. Intra-group comparison and inter-group comparison were done through the Kruskal-Wallis ANOVA test. All statistical tests were performed through SPSS version 25.0 (IBM).
UNASSIGNED: The inter-group statistical analysis concerning NRS, HI, and ET showed statistically significant results in Groups A and B compared to Group C (P < 0.05), while gingival biotype showed statistically significant results in Group A compared to Groups B and C.
UNASSIGNED: The use of PRF membrane and HA gel to protect the raw wound site of depigmented gingiva proved to be an effective approach, resulting in faster healing.

Vitiligo is a common, autoimmune, depigmenting disorder of the skin. Janus Kinase inhibitors have emerged as promising topical and oral therapeutic options for vitiligo. There have been no reports of vitiligo being treated with oral Abrocitinib, a selective Janus Kinase 1 inhibitor approved for the treatment of moderate to severe atopic dermatitis. Here, we present a 61-year-old male with acrofacial vitiligo who had repigmentation plateau with twice daily tacrolimus 0.1% ointment, oral ginkgo biloba, and oral minipulse prednisone × 4 months; however, they had significant improvement after taking abrocitinib 100 mg per day for 2 months. He was able to transition topical tacrolimus twice weekly monotherapy for maintenance. This report shows that oral Janus Kinase inhibitors may be a useful option for the treatment of recalcitrant vitiligo. Results of ongoing randomized control trials are needed to determine the durability and safety of oral Janus Kinase inhibitors long-term.

The influence of a horse\'s appearance on health, sentimental and monetary value has driven the desire to understand the etiology of coat color. White markings on the coat define inclusion for multiple horse breeds, but they may disqualify a horse from registration in other breeds. In domesticated horses (Equus caballus), 35 KIT alleles are associated with or cause depigmentation and white spotting. It is a common misconception among the general public that a horse can possess only two KIT variants. To correct this misconception, we used BEAGLE 5.4-phased NGS data to identify 15 haplotypes possessing two or more KIT variants previously associated with depigmentation phenotypes. We sourced photos for 161 horses comprising 12 compound genotypes with three or more KIT variants and employed a standardized method to grade depigmentation, yielding average white scores for each unique compound genotype. We found that 7 of the 12 multi-variant haplotypes resulted in significantly more depigmentation relative to the single-variant haplotypes (ANOVA). It is clear horses can possess more than two KIT variants, and future work aims to document phenotypic variations for each compound genotype.