title: A novel missense mutation in oncostatin M receptor beta causing primary localized cutaneous amyloidosis.
abstract: Primary localized cutaneous amyloidosis (PLCA) is a chronic skin disorder, caused by amyloid material deposition in the upper dermis. Autosomal dominant PLCA has been mapped earlier to pathogenic missense mutations in the OSMR gene, which encodes the oncostatin M receptor ß subunit (OSMRß). OSMRß is interleukin-6 family cytokine receptors and possesses two ligands, oncostatin M and interleukin-31, which both have biologic roles in inflammation and keratinocyte cell proliferation, differentiation, and apoptosis. Here, we identified a new OSMR mutation in a Kurdish family for the first time. Blood samples were taken from all the affected individuals in the family. DNA extraction was performed using salting out technique. Primers were designed for intron flanking individual exons of OSMR gene which were subjected to direct sequencing after PCR amplification for each sample. Sequencing showed a C/T substitution at position 613 in the proband. This mutation results in an L613S (leucine 613 to serine) amino acid change. The identified mutation was observed in all affected family members but not in 100 ethnically matched healthy controls. Elucidating the molecular basis of familial PLCA provides new insight into mechanisms of itch in human skin and may lead to new therapeutic targets for pruritus.
authors: Skin Research Center, Shohada-e-Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran 1989934148, Iran.
authors: Marjan
authors: 0000-0003-2427-0315
authors: M
authors: Saeedi
authors: Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran 1411413137, Iran.
authors: Azadeh
authors: 0000-0002-8993-4859
authors: A
authors: Ebrahim-Habibi
authors: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA ; Department of Medicine and the Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors: Alireza
authors: A
authors: Haghighi
authors: Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran 1411413137, Iran.
authors: Fariba
authors: F
authors: Zarrabi
authors: Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran 1411413137, Iran.
authors: Mahsa M
authors: MM
authors: Amoli
authors: Skin Research Center, Shohada-e-Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran 1989934148, Iran.
authors: Reza M
authors: RM
authors: Robati
mesh_terms: D000686:Amyloidosis / Q000235:genetics*; D017209:Apoptosis; D001706:Biopsy; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D004247:DNA / Q000737:chemistry; D005260:Female; D006801:Humans; D007249:Inflammation; D018793:Interleukin-13 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology; D007930:Leucine / Q000737:chemistry; D008297:Male; D020125:Mutation, Missense; D053683:Oncostatin M / Q000378:metabolism; D053681:Oncostatin M Receptor beta Subunit / Q000235:genetics*; D010375:Pedigree; D018121:Receptors, Cytokine / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012871:Skin Diseases / Q000235:genetics*
chemical_list: D018793:Interleukin-13; D015850:Interleukin-6; C508348:OSMR protein, human; D053681:Oncostatin M Receptor beta Subunit; D018121:Receptors, Cytokine; D053683:Oncostatin M; D004247:DNA; D007930:Leucine