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Epidermolytic ichthyosis (EI) is a type of congenital ichthyosis, characterized by erythema and blistering at birth followed by hyperkeratosis. EI is caused by pathogenic variants in the genes KRT1 and KRT10, encoding the proteins keratin 1 (KRT1) and keratin 10 (KRT10), respectively, and is primarily transmitted by autosomal‐dominant inheritance, although recessive inheritance caused by nonsense variants in KRT10 is also described. The keratins form a network of intermediate filaments and are a structural component of the cytoskeleton, giving strength and resilience to the skin. We present three cases of mild EI caused by pathogenic KRT10 variations in the L12 linker domain. To our knowledge, this is the first time L12 linker domain pathogenic variants are identified in KRT10 for EI. The aim of this study was to identify gene variants for patients with EI in KRT1 or KRT10. To establish the pathogenicity of the found variations in KRT10, we evaluated all patients and available family members clinically. Genetic analyses were performed using Sanger sequencing. Vectors containing wild‐type or mutated forms of KRT10 were transfected into HaCaT cells and analyzed by high‐resolution confocal microscopy. Genetic analysis of KRT10 identified a heterozygous de novo variant c.910G>A p.(Val304Met) in family 1, a familial heterozygous variant c.911T>C p.(Val304Ala) in family 2, and a familial heterozygous variant c.917T>C p.(Met306Thr) in family 3. All identified missense variants were located in the L12 linker domain of KRT10. In vitro study of aggregate formation of the missense variants in KRT10 only showed a very mild and not quantifiable aggregate formation in the KRT10 network, compared with the wild‐type sequence. We report three different novel missense variants in the L12 linker domain of KRT10 in patients with an atypical, milder form of EI resembling peeling skin syndrome. [ABSTRACT FROM AUTHOR]

This article discusses two cases of palmoplantar keratoderma, a skin condition characterized by thickened and hardened skin on the palms and soles. The patients presented with linear distribution of verrucous and keratotic plaques on their hands, feet, and other areas of the body. Genetic analysis revealed pathogenic variants in the HRAS gene, which is associated with various skin disorders. The article suggests that the clinical presentation of HRAS-associated nevus (HAN) can vary widely, from isolated linear palmoplantar keratoderma to widespread lesions covering the skin in a mosaic pattern. [Extracted from the article]

Linked Comment: E. Epstein. Br J Dermatol 2022; 186:203. Plain language summary available online [ABSTRACT FROM AUTHOR]

Background: Evidence on fumaric acid esters (FAE) in the treatment of pediatric psoriasis is scarce.Objective: Describe the effectiveness, influence on the quality of life (QoL) and safety of FAE in children with recalcitrant psoriasis in daily clinical practice.Methods: A prospective case series.Results: Fourteen patients with recalcitrant plaque-type psoriasis were described (mean age 13.7, range 8–17 years). Mean treatment duration was 48.6 weeks (range 12–124). Maximum daily dose varied between 180 and 1200 mg with a mean of 564 mg per day. Mean Psoriasis Area and Severity Index (PASI) (±SEM) at baseline was 10.5 (1.0) compared to 8.6 (1.1), 6.2 (1.6) and 4.9 (1.5) at week 12, 24 and 36, respectively. An improvement in PASI was observed in nine patients (64.3%). Mean CDLQI (±SEM) at week 0, 12, 24 and 36 was 8.9 (1.4), 6.8 (1.2), 3.7 (1.4) and 3.1 (2.0), respectively. Most common adverse events (AEs) were gastrointestinal complaints (n = 13, 92.9%) and flushes (n = 10, 71.4%). Lymphocytopenia (n = 5, 45.5%) and eosinophilia (n = 4, 36.4%) were frequently observed laboratory abnormalities. AEs were usually mild and transient. One serious adverse event, unrelated to FAE, was reported.Conclusions: FAE showed improvement of disease severity and QoL in the majority of children. Side-effects occurred frequently, but were usually mild and transient. FAE may be an alternative systemic treatment option for pediatric psoriasis, provided that also the long-term safety data are closely monitored, in particular lymphocytopenia. [ABSTRACT FROM AUTHOR]

Background: The Psoriasis Area and Severity Index (PASI) is not able to measure small affected areas in a body region which is important for assessing the performance of high-effective treatment. Objective: To present the Low PASI score, show the difference between the classic PASI and the Low PASI, evaluate the inter-observer agreement of both scores, and compare the two scores within investigators. Methods: Cross-sectional study. Two investigators independently assessed the classic PASI and the Low PASI in 10 patients with mild-to-moderate plaque psoriasis. Differences in outcome between the two scores were calculated. Intra-class correlation coefficients (ICC) were used to determine the inter-observer agreement and to compare measurements of the two scores within both investigators. Prediction limits of 95% for the errors in measurements were provided. Results: In both investigators, Low PASI was mean 1.71 and 1.76, whereas the classic PASI was mean 4.14 and 4.33. The inter-observer agreement (ICC) was excellent for both investigators in both scores (ICC classic PASI = 0.95 and Low PASI = 0.87). Conclusion: The Low PASI score allows more possible scores at lower levels of psoriasis extent (affected areas lower than 10% in a body region) compared to the classic PASI. This new score may lead to a more precise analysis of treatment responses and may have important clinical implications. [ABSTRACT FROM PUBLISHER]

The article presents a case study of a girl having mild phenotype of congenital ichthyosis and hypotrichosis which is linked to a new mutation in CDLN1. The hair of the patient was extremenly brittle and she did not have eyelashes or eyebrows. Her mother reported that enamel of her milk teeth was previously dysplastic.

Objectives: This study concerns Chinese mothers' color-conscious socialization and social dominance orientation and how these relate to children's racial attitudes., Method: Data were collected from a sample of 155 Chinese children (71 girls) aged 7-11 years and their mothers, from urban regions across China (Shanghai, Jinan, and cities in Jiangsu Province), including observations of mothers' color-conscious practices, self-reported social dominance orientation, and children's attitudes toward light-skinned Chinese, tan-skinned Chinese, and White groups. All children were born in urban areas and from middle-income families., Results: Variable- and person-centered analyses suggested three areas of color-conscious practices, racial appearance, cultural background, and grouping, and revealed heterogeneity in associations between color consciousness and social dominance orientation. Mothers' acknowledgment of shared culture was associated with children's positive attitudes toward their racial ingroup with darker skin tone., Conclusions: This study emphasizes the importance of a nuanced and contextualized understanding of color-conscious socialization. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Social Misfit Theory, which states that some individuals deviate from what is normative in a community and may therefore be more likely to be victimized, has mostly been studied in Western countries. The current study addresses in a longitudinal sample whether socio-economic minorities (SES) in the classroom (a contextual SES minority) are more likely to become victims of bullying in India, and whether the relation between minority status and victimization is mediated by perception of oneself as a minority. The current study used three waves separated by three month intervals. A sample of youth from Indore India (grades 7 to 9; N = 1238; M-age T1  = 13.15, SD = 1.16, 24 percent girls) was used. It was found that being a contextual SES minority was related to more victimization, but only when the contextual status was corroborated by the perceived minority status. However, over time, being part of a contextual minority predicted decreased victimization, possibly pointing to normative beliefs and values in the Indian context. The results of this study are in contrast to the Social Misfit Theory, but do support self-perception as a mediator., (© 2024. The Author(s).)

Background: Pathogenic variants in filaggrin (FLG) are associated with an increased risk of atopic dermatitis (AD)., Objective: We evaluated the influence of FLG variants on the effectiveness of dupilumab treatment in AD., Methods: This prospective observational study included adult AD patients treated with dupilumab from the BioDay registry. FLG was analyzed with single-molecule molecular inversion probe-targeted sequencing. Novel mutations were confirmed by Sanger sequencing. Eczema Area and Severity Index (EASI), Investigator Global Assessment (IGA), numeric rating scale (NRS) pruritus, Dermatology Quality of Life Index (DLQI), and Patient-Oriented Eczema Measure (POEM) were assessed at baseline and at weeks 16 and 52. The study was registered at ClinicalTrials.gov as NCT03549416., Results: Genetic analysis of the 285 included patients showed biallelic pathogenic variants (FLG -/- ) in 41 (14%), monoallelic pathogenic variants (FLG -/+ ) in 64 (23%), and wild-type alleles (FLG +/+ ) in 180 patients (63%). Three novel pathogenic variants were found. We observed no clinically relevant differences in EASI, IGA, NRS pruritus, DLQI, or total POEM scores for patients with and without pathogenic FLG variants at all time points. The FLG -/- group showed significantly higher POEM flaking and dryness scores at week 16 (P < .001 and P = .002, respectively) and week 52 (P < .001 and P = .016, respectively) compared to FLG +/+ as well as significant differences compared to FLG -/+ , while differences in delta scores were nonsignificant., Conclusion: The effectiveness of dupilumab treatment in AD patients was not influenced by pathogenic FLG variants. However, patients with biallelic pathogenic FLG variants tended to have drier skin before and during dupilumab treatment compared to patients with monoallelic pathogenic variants or wild-type alleles., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Genome diagnostics is considered gold standard diagnostics for epidermolysis bullosa (EB), a phenotypically and genetically heterogeneous group of rare disorders characterized by blistering and wounding of mucocutaneous tissues. EB is caused by pathogenic variants in genes encoding proteins of the dermo-epidermal junction. Accurate genetic diagnosis of EB is crucial for prognostication, counselling and precision-medicine. Genome diagnostics for EB started in 1991 with the introduction of Sanger sequencing (SS), analysing one gene at a time. In 2013, SS was superseded by next-generation sequencing (NGS), that allow for high-throughput sequencing of multiple genes in parallel. Several studies have shown a beneficial role for NGS in EB diagnostics, but its true benefit has not been quantified., Objectives: To determine the benefit of NGS in EB by systematically evaluating the performance of different genome diagnostics used over time based on robust data from the Dutch EB Registry., Methods: The diagnostic performances of SS and NGS were systematically evaluated in a retrospective observational study including all index cases with a clinical diagnosis of EB in whom genome diagnostics was performed between 01 January 1994 and 01 January 2022 (n = 308), registered at the Dutch EB Expertise Centre., Results: Over time, a genetic diagnosis was made in 289/308 (94%) EB cases. The diagnostic yield increased from 89% (SS) to 95% (NGS). Most importantly, NGS significantly reduced diagnostic turnaround time (39 days vs. 211 days, p < 0.001). The likelihood of detecting variants of uncertain significance and additional findings increased from 5% and 1% (SS) to 22% and 13% (NGS) respectively., Conclusions: Our study quantifies the benefit of NGS-based methods and demonstrate they have had a major impact on EB diagnostics through an increased diagnostic yield and a dramatically decreased turnaround time (39 days). Although our diagnostic yield is high (95%), further improvement of genome diagnostics is urgently needed to provide a genetic diagnosis in all EB patients., (© 2024 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Basal cell nevus syndrome (BCNS) is an inherited disorder characterized mainly by the development of basal cell carcinomas (BCCs) at an early age. BCNS is caused by heterozygous small-nucleotide variants (SNVs) and copy-number variants (CNVs) in the Patched1 ( PTCH1 ) gene. Genetic diagnosis may be complicated in mosaic BCNS patients, as accurate SNV and CNV analysis requires high-sensitivity methods due to possible low variant allele frequencies. We compared test outcomes for PTCH1 CNV detection using multiplex ligation-probe amplification (MLPA) and digital droplet PCR (ddPCR) with samples from a BCNS patient heterozygous for a PTCH1 CNV duplication and the patient's father, suspected to have a mosaic form of BCNS. ddPCR detected a significantly increased PTCH1 copy-number ratio in the index patient's blood, and the father's blood and tissues, indicating that the father was postzygotic mosaic and the index patient inherited the CNV from him. MLPA only detected the PTCH1 duplication in the index patient's blood and in hair and saliva from the mosaic father. Our data indicate that ddPCR more accurately detects CNVs, even in low-grade mosaic BCNS patients, which may be missed by MLPA. In general, quantitative ddPCR can be of added value in the genetic diagnosis of mosaic BCNS patients and in estimating the recurrence risk for offspring.