The classical recessive coat color mutation misty (m) arose spontaneously on the DBA/J background and causes generalized hypopigmentation and localized white-spotting in mice, with a lack of pigment on the belly, tail tip, and paws. Here we describe moonlight (mnlt), a second hypopigmentation and white-spotting mutation identified on the C57BL/6J background, which yields a phenotypic copy of m/m coat color traits. We demonstrate that the 2 mutations are allelic. m/m and mnlt/mnlt phenotypes both result from mutations that truncate the dedicator of cytokinesis 7 protein (DOCK7), a widely expressed Rho family guanine nucleotide exchange factor. Although Dock7 is transcribed at high levels in the developing brain and has been implicated in both axon development and myelination by in vitro studies, we find no requirement for DOCK7 in neurobehavioral function in vivo. However, DOCK7 has non-redundant role(s) related to the distribution and function of dermal and follicular melanocytes.
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http://dx.doi.org/10.1073/pnas.0813208106 | DOI Listing |
Sci Rep
January 2025
Department of Dermatology, First Affiliated Hospital of Zhengzhou University, No.1 Longhu Outer Ring Road, Jinshui District, Zhengzhou, 450052, Henan, China.
Vitiligo is a complex autoimmune disease characterized by the loss of melanocytes, leading to skin depigmentation. Despite advances in understanding its genetic and molecular basis, the precise mechanisms driving vitiligo remain elusive. Integrating multiple layers of omics data can provide a comprehensive view of disease pathogenesis and identify potential therapeutic targets.
View Article and Find Full Text PDFEur J Hum Genet
January 2025
Service de Génétique Médicale, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
Pigmentation is orchestrated by hundreds of genes involved in cellular functions going from early developmental fate of pigment cells to melanin synthesis. The Two Pore Channel 2 (TPC2) a Ca2+ and Na+ channel acidifies melanosomal pH and thus inhibits pigmentation. A young patient was recently reported with generalized hypopigmentation but uneventful ocular examination, caused by the de novo heterozygous TPCN2 variant c.
View Article and Find Full Text PDFTurk J Pediatr
November 2024
Division of Pediatric Immunology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Türkiye.
Background: Griscelli syndrome (GS) is a rare genetic disorder characterized by oculocutaneous albinism and variable immune dysfunction. Among three distinct types of GS, occurring due to different genetic mutations; GS type 1 presents with neurological manifestations, hemophagocytic lymphohistiocytosis (HLH) generally develops in GS type 2, and GS type 3 primarily exhibits oculocutaneous albinism. HLH, a life-threatening condition with excessive immune activation, may occur secondary to various triggers, including infections, and develop in different tissues, as well as in the testis, similar to Erdheim-Chester disease.
View Article and Find Full Text PDFMelanoma Res
January 2025
Department of Dermatology, Hospital Universitario y Politécnico La Fe.
Vitiligo-like hypopigmentation induced by immune checkpoint inhibitors (ICIs) has been largely associated with improved survival outcomes in metastatic melanoma. However, its development during adjuvant ICI therapy and its role as a prognostic factor in this setting remain unclear. We aimed to describe ICI-induced vitiligo in a cohort of patients with resected stage III melanoma treated with adjuvant ICI and to identify differences in progression-free survival (PFS) and distant metastasis-free survival (DMFS) between those who developed vitiligo and those who did not.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Dermatology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Biological drugs are extensively used to treat various inflammatory diseases, including psoriasis, atopic dermatitis (AD), and rheumatoid arthritis. While generally effective and safe, these therapies have been increasingly associated with secondary development of vitiligo, especially with anti-TNF α and anti-IL17 drugs. Dupilumab, an IL-4 receptor alpha antagonist used in moderate to severe AD, rarely induces vitiligo.
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