Search Results (5)

Galli–Galli disease (GGD) is a rare genodermatosis that exhibits autosomal dominant inheritance with variable penetrance. GGD typically manifests with erythematous macules, papules, and reticulate hyperpigmentation in flexural areas. A distinct atypical variant exists, which features brown macules predominantly on the trunk, lower limbs, and extremities, with a notable absence of the hallmark reticulated hyperpigmentation in flexural areas. This review includes a detailed literature search and examines cases since GGD’s first description in 1982. It aims to synthesize the current knowledge on GGD, covering its etiology, clinical presentation, histopathology, diagnosis, and treatment. A significant aspect of this review is the exploration of the genetic, histopathological, and clinical parallels between GGD and Dowling-Degos disease (DDD), which is another rare autosomal dominant genodermatosis, particularly focusing on their shared mutations in the KRT5 and POGLUT1 genes. This supports the hypothesis that GGD and DDD may be different phenotypic expressions of the same pathological condition, although they have traditionally been recognized as separate entities, with suprabasal acantholysis being a distinctive feature of GGD. Lastly, this review discusses the existing treatment approaches, underscoring the absence of established guidelines and the limited effectiveness of various treatments. Full article

Reticulate pigmentary disorders (RPDs) are a group of inherited and acquired skin conditions characterized by hyperpigmented and/or hypopigmented macules. Inherited RPDs include dyschromatosis symmetrica hereditaria (DSH), dyschromatosis universalis hereditaria (DUH), reticulate acropigmentation of Kitamura (RAK), Dowling-Degos disease (DDD), dyskeratosis congenita (DKC), Naegeli–Franceschetti–Jadassohn syndrome (NFJS), dermatopathia pigmentosa reticularis (DPR), and X-linked reticulate pigmentary disorder. Although reticulate pattern of pigmentation is a common characteristic of this spectrum of disorders, the distribution of pigmentation varies among these disorders, and there may be clinical manifestations beyond pigmentation. DSH, DUH, and RAK are mostly reported in East Asian ethnicities. DDD is more common in Caucasians, although it is also reported in Asian countries. Other RPDs show no racial predilection. This article reviews the clinical, histological, and genetic variations of inherited RPDs. Full article

Alterations in genes encoding for proteins that control fucosylation are known to play causative roles in several developmental disorders, such as Dowling-Degos disease 2 and congenital disorder of glycosylation type IIc (CDGIIc). Recent studies have provided evidence that changes in fucosylation can contribute to the development and progression of several different types of cancers. It is therefore important to gain a detailed understanding of how fucosylation is altered in disease states so that interventions may be developed for therapeutic purposes. In this report, we find that fucosylation occurs on many intracellular proteins. This is an interesting finding, as the fucosylation machinery is restricted to the secretory pathway and is thought to predominately affect cell-membrane-bound and secreted proteins. We find that Ribosomal protein S3 (RPS3) is fucosylated in normal tissues and in cancer cells, and that the extent of its fucosylation appears to respond to stress, including MAPK inhibitors, suggesting a new role in posttranslational protein function. Our data identify a new ribosome-independent species of fucosylated RPS3 that interacts with proteins involved in posttranscriptional regulation of RNA, such as Heterogeneous nuclear ribonucleoprotein U (HNRNPU), as well as with a predominance of non-coding RNAs. These data highlight a novel role for RPS3, which, given previously reported oncogenic roles for RPS3, might represent functions that are perturbed in pathologies such as cancer. Together, our findings suggest a previously unrecognized role for fucosylation in directly influencing intracellular protein functions. Full article

The high volume of information produced in the age of omics was and still is an important step to understanding several pathological processes, providing the enlightenment of complex molecular networks and the identification of molecular targets associated with many diseases. Despite these remarkable scientific advances, the majority of the results are disconnected and divergent, making their use limited. Skin diseases with alterations in the Notch signaling pathway were extensively studied during the omics era. In the GWAS Catalog, considering only studies on genomics association (GWAS), several works were deposited, some of which with divergent results. In addition, there are thousands of scientific articles available about these skin diseases. In our study, we focused our attention on skin diseases characterized by the impairment of Notch signaling, this pathway being of pivotal importance in the context of epithelial disorders. We considered the pathologies of five human skin diseases, Hidradenitis Suppurativa, Dowling Degos Disease, Adams–Oliver Syndrome, Psoriasis, and Atopic Dermatitis, in which the molecular alterations in the Notch signaling pathway have been reported. To this end, we started developing a new multiomics platform, PlatOMICs, to integrate and re-analyze omics information, searching for the molecular interactions involved in the pathogenesis of skin diseases with alterations in the Notch signaling pathway. Full article

Notch signaling orchestrates the regulation of cell proliferation, differentiation, migration and apoptosis of epidermal cells by strictly interacting with other cellular pathways. Any disruption of Notch signaling, either due to direct mutations or to an aberrant regulation of genes involved in the signaling route, might lead to both hyper- or hypo-activation of Notch signaling molecules and of target genes, ultimately inducing the onset of skin diseases. The mechanisms through which Notch contributes to the pathogenesis of skin diseases are multiple and still not fully understood. So far, Notch signaling alterations have been reported for five human skin diseases, suggesting the involvement of Notch in their pathogenesis: Hidradenitis Suppurativa, Dowling Degos Disease, Adams–Oliver Syndrome, Psoriasis and Atopic Dermatitis. In this review, we aim at describing the role of Notch signaling in the skin, particularly focusing on the principal consequences associated with its alterations in these five human skin diseases, in order to reorganize the current knowledge and to identify potential cellular mechanisms in common between these pathologies. Full article