Familial chilblain lupus (FCL);
Chilblain lupus erythematosus (CHLE)

Familial chilblain lupus (FCL) is a rare, inherited form of cutaneous lupus with prominent skin manifestations in acral parts of the body. Two families with autosomal dominant-inherited chilblain lupus have been reported. First symptoms manifest in early childhood, developing hypergammaglobulinemia and rheumatoid factor antibody production. In FCL, missense mutations in TREX1 that decrease its exonuclease activity were described. The failure of DNA degradation can result in aberrant immune response.

Immune system disease

TREX1 [HSA:11277] [KO:K10790]

cold and wet exposure

PMID:18543054

Hedrich CM, Fiebig B, Hauck FH, Sallmann S, Hahn G, Pfeiffer C, Heubner G, Lee-Kirsch MA, Gahr M

Chilblain lupus erythematosus--a review of literature.

Clin Rheumatol 27:949-54 (2008)
DOI:10.1007/s10067-008-0942-9

PMID:18583934

Kavanagh D, Spitzer D, Kothari PH, Shaikh A, Liszewski MK, Richards A, Atkinson JP

New roles for the major human 3'-5' exonuclease TREX1 in human disease.

Cell Cycle 7:1718-25 (2008)
DOI:10.4161/cc.7.12.6162

PMID:17357087

Rice G, Newman WG, Dean J, Patrick T, Parmar R, Flintoff K, Robins P, Harvey S, Hollis T, O'Hara A, Herrick AL, Bowden AP, Perrino FW, Lindahl T, Barnes DE, Crow YJ

Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi-Goutieres syndrome.

Am J Hum Genet 80:811-5 (2007)
DOI:10.1086/513443

PMID:17440703

Lee-Kirsch MA, Chowdhury D, Harvey S, Gong M, Senenko L, Engel K, Pfeiffer C, Hollis T, Gahr M, Perrino FW, Lieberman J, Hubner N

A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus.

J Mol Med 85:531-7 (2007)
DOI:10.1007/s00109-007-0199-9

PMID:19478477

Gunther C, Meurer M, Stein A, Viehweg A, Lee-Kirsch MA

Familial chilblain lupus--a monogenic form of cutaneous lupus erythematosus due to a heterozygous mutation in TREX1.

Dermatology 219:162-6 (2009)
DOI:10.1159/000222430