title: Novel IL31RA gene mutation and ancestral OSMR mutant allele in familial primary cutaneous amyloidosis.
abstract: Primary cutaneous amyloidosis (PCA) is an itchy skin disorder associated with amyloid deposits in the superficial dermis. The disease is relatively common in Southeast Asia and South America. Autosomal dominant PCA has been mapped earlier to 5p13.1-q11.2 and two pathogenic missense mutations in the OSMR gene, which encodes the interleukin-6 family cytokine receptor oncostatin M receptor beta (OSMRbeta), were reported. Here, we investigated 29 Taiwanese pedigrees with PCA and found that 10 had heterozygous missense mutations in OSMR: p.D647V (one family), p.P694L (six families), and p.K697T (three families). The mutation p.P694L was associated with the same haplotype in five of six families and also detected in two sporadic cases of PCA. Of the other 19 pedigrees that lacked OSMR pathology, 8 mapped to the same locus on chromosome 5, which also contains the genes for 3 other interleukin-6 family cytokine receptors, including interleukin-31 receptor A (IL31RA), which can form a heterodimeric receptor with OSMRbeta through interleukin-31 signaling. In one family, we identified a point mutation in the IL31RA gene, c.1562C>T that results in a missense mutation, p.S521F, which is also sited within a fibronectin type III-like repeat domain as observed in the OSMR mutations. PCA is a genetically heterogeneous disorder but our study shows that it can be caused by mutations in two biologically associated cytokine receptor genes located on chromosome 5. The identification of OSMR and IL31RA gene pathology provides an explanation of the high prevalence of PCA in Taiwan as well as new insight into disease pathophysiology.
authors.affiliation: Institute of Public Health, National Yang-Ming University, No. 155, Section 2, LiNong Street, Beitou, Taipei 112, Taiwan. mwlin@ym.edu.tw
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Lin
authors.forename: Ding-Dar
authors.initials: DD
authors.lastname: Lee
authors.forename: Tze-Tze
authors.initials: TT
authors.lastname: Liu
authors.forename: Yong-Feng
authors.initials: YF
authors.lastname: Lin
authors.forename: Shang-Yi
authors.initials: SY
authors.lastname: Chen
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Huang
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Weng
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Liu
authors.forename: Akio
authors.initials: A
authors.lastname: Tanaka
authors.forename: Ken
authors.initials: K
authors.lastname: Arita
authors.forename: Joey
authors.initials: J
authors.lastname: Lai-Cheong
authors.forename: Francis
authors.initials: F
authors.lastname: Palisson
authors.forename: Yun-Ting
authors.initials: YT
authors.lastname: Chang
authors.forename: Chu-Kwan
authors.initials: CK
authors.lastname: Wong
authors.forename: Isao
authors.initials: I
authors.lastname: Matsuura
authors.forename: John A
authors.initials: JA
authors.lastname: McGrath
authors.forename: Shih-Feng
authors.initials: SF
authors.lastname: Tsai
mesh_terms: D000483:Alleles; D028226:Amyloidosis, Familial / Q000235:genetics*; D001483:Base Sequence; D002677:Chile; D004252:DNA Mutational Analysis; D008040:Genetic Linkage; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D053681:Oncostatin M Receptor beta Subunit / Q000235:genetics*; D010802:Phylogeny; D018123:Receptors, Interleukin / Q000235:genetics*; D015203:Reproducibility of Results; D012871:Skin Diseases / Q000235:genetics*; D013624:Taiwan
chemical_list: C502188:IL31RA protein, human; D050505:Mutant Proteins; C508348:OSMR protein, human; D053681:Oncostatin M Receptor beta Subunit; D018123:Receptors, Interleukin
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