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Nature Communications Jun 2024Evidence for adaptation of human skin color to regional ultraviolet radiation suggests shared and distinct genetic variants across populations. However, skin color...
Evidence for adaptation of human skin color to regional ultraviolet radiation suggests shared and distinct genetic variants across populations. However, skin color evolution and genetics in East Asians are understudied. We quantified skin color in 48,433 East Asians using image analysis and identified associated genetic variants and potential causal genes for skin color as well as their polygenic interplay with sun exposure. This genome-wide association study (GWAS) identified 12 known and 11 previously unreported loci and SNP-based heritability was 23-24%. Potential causal genes were determined through the identification of nonsynonymous variants, colocalization with gene expression in skin tissues, and expression levels in melanocytes. Genomic loci associated with pigmentation in East Asians substantially diverged from European populations, and we detected signatures of polygenic adaptation. This large GWAS for objectively quantified skin color in an East Asian population improves understanding of the genetic architecture and polygenic adaptation of skin color and prioritizes potential causal genes.
Topics: Adult; Female; Humans; Male; Middle Aged; Adaptation, Physiological; Chromosome Mapping; Genome-Wide Association Study; Multifactorial Inheritance; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Skin Pigmentation; Ultraviolet Rays; East Asian People
PubMed: 38849341
DOI: 10.1038/s41467-024-49031-4 -
The Journal of Investigative Dermatology Jun 2024A better understanding of human melanocyte (MC) and melanocyte stem cell (McSC) biology is essential for treating melanocyte-related diseases. This study employed an...
A better understanding of human melanocyte (MC) and melanocyte stem cell (McSC) biology is essential for treating melanocyte-related diseases. This study employed an inherited pigmentation disorder carrying the SASH1 variant in a Hispanic family to investigate the SASH1 function in the MC lineage and the underlying mechanism for this disorder. We used a multidisciplinary approach, including clinical exams, human cell assays, yeast two-hybrid screening, and biochemical techniques. Results linked early hair graying to the SASH1 variant, a previously unrecognized clinical phenotype in hyperpigmentation disorders. In vitro, we identified SASH1 as a regulator in McSC maintenance and discovered that TNKS2 is crucial for SASH1's role. Additionally, the S519N variant is located in one of multiple tankyrase-binding motifs and alters the binding kinetics and affinity of the interaction. In summary, this disorder links both gain and loss of pigmentation in the same individual, hinting to accelerated aging in human McSC. The findings offer insights into the roles of SASH1 and TNKS2 in McSC maintenance and the molecular mechanisms of pigmentation disorders. We propose that a comprehensive clinical evaluation of patients with MC-related disorders should include an assessment and history of hair pigmentation loss.
PubMed: 38848986
DOI: 10.1016/j.jid.2024.04.027 -
Indian Journal of Dermatology 2024Vitiligo is characterized by depigmentation due to melanocyte destruction. Itch is an under-recognized symptom; its pathophysiology is unclear.
BACKGROUND
Vitiligo is characterized by depigmentation due to melanocyte destruction. Itch is an under-recognized symptom; its pathophysiology is unclear.
AIMS
To compare epidermal biophysical characteristics of the vitiligous skin and normal skin and to determine the association with thyroid auto-immunity and itch.
METHODS
A cross-sectional study involving vitiligo patients was conducted. Hydration, pH, and trans-epidermal water loss (TEWL) at the vitiligous skin and normal adjacent skin were measured. The Vitiligo Disease Activity Score (VIDA) and Vitiligo Area Scoring Index (VASI) were assessed. Itch severity and thyroid auto-antibodies were determined.
RESULTS
Thirty-nine (62.9%) females and 23 (37.1%) males participated. Twenty-six (41.9%) had stable vitiligo, and 36 (58.1%) had active disease with a median VASI was 0.8 (2.2). Hydration was lower [93 (83) to 125.5 (111) vs 104 (73) to 156 (100), < 0.01] and TEWL [7.13 (6.18) to 8.86 (6.93) vs 5.54 (5.90) to 6.88 (6.37), < 0.01] was higher at the vitiligous skin compared to the normal skin. A non-significant higher pH trend was observed in the vitiligous skin. Thyroid antibody was detected in 19.7% patients. There were no significant differences in biophysical characteristics between patients with and without thyroid antibodies, with hydration of 88 (159) to 129.5 (120) vs 91.5 (81) to 116 (101) and TEWL of 7.08 (2.03) to 9.97 (6.38) vs 7.65 (7.54) to 8.22 (6.52). Itch was reported by 14 (22.6%). Patients with itch had lower hydration and higher TEWL but were not significantly different from patients without itch.
CONCLUSIONS
The vitiligous skin has reduced hydration and increased TEWL, suggesting a defective epidermal barrier. Thyroid antibody positivity was not associated with biophysical characteristics or itch. Itch was not associated with hydration, pH, and TEWL. An impaired epidermal barrier and itch need to be addressed in vitiligo management.
PubMed: 38841249
DOI: 10.4103/ijd.ijd_785_23 -
Australian Journal of General Practice Jun 2024General practitioners manage a significant proportion of inflammatory and neoplastic skin conditions on a daily basis. Various surgical techniques can be employed to aid...
BACKGROUND
General practitioners manage a significant proportion of inflammatory and neoplastic skin conditions on a daily basis. Various surgical techniques can be employed to aid in diagnosis, including punch biopsies, shave biopsy, shave excision, incisional biopsy, curettage and formal excision with closure. Requiring minimal equipment, shave procedures are quick to perform, produce good cosmetic outcomes and minimise costs.
OBJECTIVE
Our aim is to discuss shave procedures in detail and highlight the difference between shave biopsies and shave excisions, as well as the role they each have in diagnosing an array of benign, inflammatory and malignant skin conditions, including melanocytic lesions.
DISCUSSION
Shave procedures performed on suitable lesions by trained practitioners can be used for sampling or removing suspect lesions. Where the intent is complete removal, margin involvement is rare given good lesion selection and technique.
Topics: Humans; General Practice; Biopsy; Skin Diseases
PubMed: 38840380
DOI: 10.31128/AJGP-06-23-6872 -
Anais Brasileiros de Dermatologia Jun 2024
PubMed: 38834397
DOI: 10.1016/j.abd.2023.05.011 -
Peptides Jun 2024The central and peripheral melanocortin system, comprising of five receptors and their endogenous ligands, is responsible for a wide array of physiological functions...
The central and peripheral melanocortin system, comprising of five receptors and their endogenous ligands, is responsible for a wide array of physiological functions such as skin pigmentation, sexual function and development, and inflammation. A growing body of both clinical and pre-clinical research is demonstrating the relevance of this system in metabolic health. Disruption of hypothalamic melanocortin signalling is the most common cause of monogenic obesity in humans. Setmelanotide, an FDA-approved analogue of alpha-melanocyte stimulating hormone (α-MSH) that functions by restoring central melanocortin signalling, has proven to be a potent pharmacological tool in the treatment of syndromic obesity. As the first effective therapy targeting the melanocortin system to treat metabolic disorders, its approval has sparked research to further harness the links between these melanocortin receptors and metabolic processes. Here, we outline the structure of the central and peripheral melanocortin system, discuss its critical role in the regulation of food intake, and review promising targets that may hold potential to treat metabolic disorders in humans.
PubMed: 38834138
DOI: 10.1016/j.peptides.2024.171255 -
Case Reports in Dermatology 2024The development of new and changing melanocytic lesions has been increasingly reported as an adverse dermatologic toxicity of BRAF inhibitor therapy. Melanocytic lesions...
INTRODUCTION
The development of new and changing melanocytic lesions has been increasingly reported as an adverse dermatologic toxicity of BRAF inhibitor therapy. Melanocytic lesions and melanomas induced by BRAF inhibitor therapy that lack V600E expression have been less commonly described. One mechanism that has been proposed for the development of BRAF inhibitor-induced melanocytic lesions, including those lacking V600E expression, is the paradoxical activation of the MAPK signaling pathway in wild-type () cells.
CASE PRESENTATION
Herein, we report a rare case of a 39-year-old woman who developed numerous V600E-negative eruptive melanocytic nevi following encorafenib, cetuximab, and binimetinib combination therapy, the current standard of care for the treatment of -mutant metastatic colorectal cancer.
CONCLUSION
Patients treated with BRAF inhibitors, with or without related combination therapies, who develop melanocytic lesions are at risk for developing both dysplastic nevi and melanoma, thereby warranting baseline dermatoscopic evaluation prior to the initiation of therapy as well as regular follow-up during and after treatment.
PubMed: 38831934
DOI: 10.1159/000539058 -
Urology Case Reports May 2024BCRA-associated protein-1 (BAP-1) mutation has been associated with the development of a familiar syndrome that predisposes to tumors with a higher incidence than in...
BCRA-associated protein-1 (BAP-1) mutation has been associated with the development of a familiar syndrome that predisposes to tumors with a higher incidence than in general population, including melanoma and renal carcinoma. We report a 47-year-old woman diagnosed with a BAPoma (melanocytic tumor characterized by the loss of BAP-1). Due to her extensive family history with multiple neoplasms, a FDG PET-CT was performed. Consequently, she was diagnosed with an atypical renal mass, which is rarely linked to this syndrome. We review and discuss the available literature on the screening, diagnosis and treatment of renal tumors associated with BAP-1 tumor predisposition syndrome.
PubMed: 38827530
DOI: 10.1016/j.eucr.2024.102700 -
Anais Brasileiros de Dermatologia May 2024
PubMed: 38824098
DOI: 10.1016/j.abd.2023.08.015 -
PloS One 2024Imaging mass spectrometry (IMS) provides promising avenues to augment histopathological investigation with rich spatio-molecular information. We have previously...
Imaging mass spectrometry (IMS) provides promising avenues to augment histopathological investigation with rich spatio-molecular information. We have previously developed a classification model to differentiate melanoma from nevi lesions based on IMS protein data, a task that is challenging solely by histopathologic evaluation. Most IMS-focused studies collect microscopy in tandem with IMS data, but this microscopy data is generally omitted in downstream data analysis. Microscopy, nevertheless, forms the basis for traditional histopathology and thus contains invaluable morphological information. In this work, we developed a multimodal classification pipeline that uses deep learning, in the form of a pre-trained artificial neural network, to extract the meaningful morphological features from histopathological images, and combine it with the IMS data. To test whether this deep learning-based classification strategy can improve on our previous results in classification of melanocytic neoplasia, we utilized MALDI IMS data with collected serial H&E stained sections for 331 patients, and compared this multimodal classification pipeline to classifiers using either exclusively microscopy or IMS data. The multimodal pipeline achieved the best performance, with ROC-AUCs of 0.968 vs. 0.938 vs. 0.931 for the multimodal, unimodal microscopy and unimodal IMS pipelines respectively. Due to the use of a pre-trained network to perform the morphological feature extraction, this pipeline does not require any training on large amounts of microscopy data. As such, this framework can be readily applied to improve classification performance in other experimental settings where microscopy data is acquired in tandem with IMS experiments.
Topics: Melanoma; Humans; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Skin Neoplasms; Neural Networks, Computer; Deep Learning; Multimodal Imaging
PubMed: 38820337
DOI: 10.1371/journal.pone.0304709