title: Oncostatin M receptor-beta mutations underlie familial primary localized cutaneous amyloidosis.
abstract: 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.
authors.affiliation: Genetic Skin Disease Group, St. John's Institute of Dermatology, Division of Genetics and Molecular Medicine, The Guy's, King's College and St Thomas' School of Medicine, London SE1 9RT, UK.
authors.forename: Ken
authors.initials: K
authors.lastname: Arita
authors.forename: Andrew P
authors.initials: AP
authors.lastname: South
authors.forename: Günter
authors.initials: G
authors.lastname: Hans-Filho
authors.forename: Thais Harumi
authors.initials: TH
authors.lastname: Sakuma
authors.forename: Joey
authors.initials: J
authors.lastname: Lai-Cheong
authors.forename: Suzanne
authors.initials: S
authors.lastname: Clements
authors.forename: Maçanori
authors.initials: M
authors.lastname: Odashiro
authors.forename: Danilo Nakao
authors.initials: DN
authors.lastname: Odashiro
authors.forename: Günter
authors.initials: G
authors.lastname: Hans-Neto
authors.forename: Nelise Ritter
authors.initials: NR
authors.lastname: Hans
authors.forename: Maxine V
authors.initials: MV
authors.lastname: Holder
authors.forename: Balbir S
authors.initials: BS
authors.lastname: Bhogal
authors.forename: Sian T
authors.initials: ST
authors.lastname: Hartshorne
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.forename: John A
authors.initials: JA
authors.lastname: McGrath
mesh_terms: D000595:Amino Acid Sequence; D028226:Amyloidosis, Familial / Q000235:genetics* / Q000473:pathology; D001938:Brazil; D018929:Cell Culture Techniques; D002895:Chromosomes, Human, Pair 5; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D015603:Keratinocytes; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D053681:Oncostatin M Receptor beta Subunit / Q000737:chemistry / Q000235:genetics*; D010375:Pedigree; D017385:Sequence Homology; D013019:South Africa; D006113:United Kingdom
chemical_list: C508348:OSMR protein, human; D053681:Oncostatin M Receptor beta Subunit