Novel IL31RA gene mutation and ancestral OSMR mutant allele in familial primary cutaneous amyloidosis.
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.
Lin
Ming-Wei
MW
Institute of Public Health, National Yang-Ming University, No. 155, Section 2, LiNong Street, Beitou, Taipei 112, Taiwan. mwlin@ym.edu.tw
Lee
Ding-Dar
DD
Liu
Tze-Tze
TT
Lin
Yong-Feng
YF
Chen
Shang-Yi
SY
Huang
Chih-Cheng
CC
Weng
Hui-Ying
HY
Liu
Yu-Fen
YF
Tanaka
Akio
A
Arita
Ken
K
Lai-Cheong
Joey
J
Palisson
Francis
F
Chang
Yun-Ting
YT
Wong
Chu-Kwan
CK
Matsuura
Isao
I
McGrath
John A
JA
Tsai
Shih-Feng
SF
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
C502188:IL31RA protein, human; D050505:Mutant Proteins; C508348:OSMR protein, human; D053681:Oncostatin M Receptor beta Subunit; D018123:Receptors, Interleukin
Nat Immunol. 2004 Jul;5(7):752-60
15184896
J Immunol. 2007 Apr 1;178(7):4615-22
17372020
Clin Dermatol. 1990 Apr-Jun;8(2):20-4
2224732
Nat Genet. 2006 Mar;38(3):375-81
16493422
Br J Dermatol. 1972 Aug;87(2):123-9
5057380
Bioinformatics. 2004 May 22;20(8):1325-6
14871868
Clin Dermatol. 1990 Apr-Jun;8(2):25-9
2224733
J Neurosci. 2004 Feb 25;24(8):1941-7
14985435
Eur J Biochem. 2002 Jun;269(11):2716-26
12047380
Rev Hosp Clin Fac Med Sao Paulo. 1963 Sep-Oct;18:413-7
14113337
Eur J Neurosci. 2003 Jun;17(11):2287-98
12814362
Am J Hum Genet. 1996 Jun;58(6):1347-63
8651312
Br J Dermatol. 2006 Dec;155(6):1201-8
17107390
Clin Exp Dermatol. 1999 Nov;24(6):438-42
10606942
Br J Dermatol. 1999 Feb;140(2):210-5
10733268
Am J Hum Genet. 2008 Jan;82(1):73-80
18179886
Int J Dermatol. 1984 Apr;23(3):190-3
6724776
J Immunol. 2000 Jan 1;164(1):273-82
10605021
Br J Dermatol. 2005 Jan;152(1):29-36
15656797
Zhonghua Yi Xue Za Zhi (Taipei). 2001 Feb;64(2):101-7
11355326
Bioinformatics. 2002 Dec;18(12):1694-5
12490459
Am J Hum Genet. 1985 May;37(3):482-98
3859205
Bioinformatics. 2005 Jan 15;21(2):263-5
15297300
J Allergy Clin Immunol. 2006 Feb;117(2):411-7
16461142
Arch Dermatol. 1974 Sep;110(3):438-40
4451393
Arch Dermatol. 1978 Aug;114(8):1173-6
354533
Scand J Immunol. 2006 May;63(5):321-9
16640655
Int J Dermatol. 1988 Jun;27(5):302-7
3391726
Arch Dermatol. 1963 Feb;87:171-5
13976058
J Invest Dermatol. 1996 Jul;107(1):30-3
8752835
Br J Dermatol. 1997 Jun;136(6):823-6
9217811
Biochem J. 2003 Aug 15;374(Pt 1):1-20
12773095
Br J Dermatol. 1985 Feb;112(2):201-8
3970841
Arch Dermatol. 1981 Oct;117(10):639-43
6945068
Nature. 2003 Dec 18;426(6968):789-96
14685227
J Biol Chem. 2007 Feb 2;282(5):3014-26
17148439