title: Familial chilblain lupus, a monogenic form of cutaneous lupus erythematosus, maps to chromosome 3p.
abstract: Systemic lupus erythematosus is a prototypic autoimmune disease. Apart from rare monogenic deficiencies of complement factors, where lupuslike disease may occur in association with other autoimmune diseases or high susceptibility to bacterial infections, its etiology is multifactorial in nature. Cutaneous findings are a hallmark of the disease and manifest either alone or in association with internal-organ disease. We describe a novel genodermatosis characterized by painful bluish-red inflammatory papular or nodular lesions in acral locations such as fingers, toes, nose, cheeks, and ears. The lesions sometimes appear plaquelike and tend to ulcerate. Manifestation usually begins in early childhood and is precipitated by cold and wet exposure. Apart from arthralgias, there is no evidence for internal-organ disease or an increased susceptibility to infection. Histological findings include a deep inflammatory infiltrate with perivascular distribution and granular deposits of immunoglobulins and complement along the basement membrane. Some affected individuals show antinuclear antibodies or immune complex formation, whereas cryoglobulins or cold agglutinins are absent. Thus, the findings are consistent with chilblain lupus, a rare form of cutaneous lupus erythematosus. Investigation of a large German kindred with 18 affected members suggests a highly penetrant trait with autosomal dominant inheritance. By single-nucleotide-polymorphism-based genomewide linkage analysis, the locus was mapped to chromosome 3p. Haplotype analysis defined the locus to a 13.8-cM interval with a LOD score of 5.04. This is the first description of a monogenic form of cutaneous lupus erythematosus. Identification of the gene responsible for familial chilblain lupus may shed light on the pathogenesis of common forms of connective-tissue disease such as systemic lupus erythematosus.
authors.affiliation: Klinik fur Kinder- und Jugendmedizin, Technische Universitat Dresden, Dresden, Germany. minae.lee-kirsch@uniklinikum-dresden.de
authors.forename: Min Ae
authors.initials: MA
authors.lastname: Lee-Kirsch
authors.forename: Maolian
authors.initials: M
authors.lastname: Gong
authors.forename: Herbert
authors.initials: H
authors.lastname: Schulz
authors.forename: Franz
authors.initials: F
authors.lastname: Rüschendorf
authors.forename: Annette
authors.initials: A
authors.lastname: Stein
authors.forename: Christiane
authors.initials: C
authors.lastname: Pfeiffer
authors.forename: Annalisa
authors.initials: A
authors.lastname: Ballarini
authors.forename: Manfred
authors.initials: M
authors.lastname: Gahr
authors.forename: Norbert
authors.initials: N
authors.lastname: Hubner
authors.forename: Maja
authors.initials: M
authors.lastname: Linné
mesh_terms: D000293:Adolescent; D000936:Antigen-Antibody Complex / Q000378:metabolism; D018771:Arthralgia; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D003181:Complement C4 / Q000378:metabolism; D030541:Databases, Genetic; D005190:Family; D005260:Female; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D008178:Lupus Erythematosus, Cutaneous / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats; D020641:Polymorphism, Single Nucleotide
chemical_list: D000936:Antigen-Antibody Complex; D003181:Complement C4