Oncostatin M receptor-beta mutations underlie familial primary localized cutaneous amyloidosis

Ken Arita, Andrew P. South, Günter Hans-Filho, Thais Harumi Sakuma, Joey Lai-Cheong, Suzanne Clements, Maçanori Odashiro, Danilo Nakao Odashiro, Günter Hans-Neto, Nelise Ritter Hans, Maxine V. Holder, Balbir S. Bhogal, Sian T. Hartshorne, Masashi Akiyama, Hiroshi Shimizu, John A. McGrath

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    117 Citations (Scopus)


    Familial primary localized cutaneous amyloidosis (FPLCA) is an autosomal-dominant disorder associated with chronic skin itching and deposition of epidermal keratin filament-associated amyloid material in the dermis. FPLCA has been mapped to 5p13.1-q11.2, and by candidate gene analysis, we identified missense mutations in the OSMR gene, encoding oncostatin M-specific receptor beta (OSMRbeta), in three families. OSMRbeta is a component of the oncostatin M (OSM) type II receptor and the interleukin (IL)-31 receptor, and cultured FPLCA keratinocytes showed reduced activation of Jak/STAT, MAPK, and PI3K/Akt pathways after OSM or IL-31 cytokine stimulation. The pathogenic amino acid substitutions are located within the extracellular fibronectin type III-like (FNIII) domains, regions critical for receptor dimerization and function. OSM and IL-31 signaling have been implicated in keratinocyte cell proliferation, differentiation, apoptosis, and inflammation, but our OSMR data in individuals with FPLCA represent the first human germline mutations in this cytokine receptor complex and provide new insight into mechanisms of skin itching.
    Original languageEnglish
    Pages (from-to)73-80
    Number of pages8
    JournalAmerican Journal of Human Genetics
    Issue number1
    Publication statusPublished - 2008


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