Abstract
Dyschromatosis universalis hereditaria (DUH) is a rare genodermatosis characterized by hyper- and hypopigmented macules which form a reticulate or mottled pattern. The causal gene and the precise pathogenesis of DUH have been unclear since the disease was initially reported in 1933. However, we found three heterozygous mutations encoding amino acid substitutions in SASH1 in each of three nonconsanguineous DUH families. Immunohistochemistry and melanin staining showed distribution heterogenicity of melanocytes, predominantly melanized melanocytes in the epidermal tissues of a DUH patient. Specifically, we identified that mutations of SASH1 can up-regulate resident melanogenic proteins, transport proteins of melanosome, and induce increased mobility of melanocytes in vitro and in vivo. Furthermore, SASH1 was shown to interact with several proteins associated with melanogenesis in the MAPK signaling pathway and the endothelin signaling pathway, indicating an additional melanogenesis signaling pathway in the regulation of melanin biosynthesis. Collectively, these observations suggest that DUH is a heterogeneous disorder of increased production and transport of melanosomes caused by SASH1 mutation together with melanocyte maldistribution.
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Xing, Q., Zhou, D. & Wei, Z. Three mutations in SASH1 cause the pathogenesis of dyschromatosis universalis hereditaria (DUH). Nat Prec (2011). https://doi.org/10.1038/npre.2011.5629.1
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DOI: https://doi.org/10.1038/npre.2011.5629.1