TY - JOUR
T1 - Oncostatin M receptor-beta mutations underlie familial primary localized cutaneous amyloidosis
AU - Arita, K
AU - South, A P
AU - Hans, G
AU - Sakuma, T H
AU - Lai-Cheong, J
AU - Clements, S
AU - Odashiro, M
AU - Dashiro, D N
AU - Hans, G
AU - Hans, N R
AU - Holder, M V
AU - Bhogal, B S
AU - Hartshorne, S T
AU - Akiyama, M
AU - Shimizu, H
AU - McGrath, J A
PY - 2008/1/10
Y1 - 2008/1/10
N2 - 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 (OSMR beta), in three families. OSMR beta 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
AB - 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 (OSMR beta), in three families. OSMR beta 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
U2 - 10.1016/j.ajhg.2007.09.002
DO - 10.1016/j.ajhg.2007.09.002
M3 - Article
SN - 1537-6605
VL - 82
SP - 73
EP - 80
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 1
ER -