title: Rare variants, autoimmune disease, and arthritis.
abstract: OBJECTIVE
  We review select studies of newly discovered rare variants in autoimmune diseases with a focus on newly described monogenic disorders, rheumatoid arthritis, and systemic lupus erythematosus.
  
  
  RESULTS
  Two new monogenic syndromes of inflammatory arthritis were discovered using whole exome sequencing: the coatomer subunit alpha syndrome because of rare mutations in coatomer subunit alpha and haploinsufficiency of A20 resulting from rare mutations in TNFAIP3. Targeted exon sequencing identified rare variants in IL2RA and IL2RB associated with rheumatoid arthritis. Rare variants in TREX1 and other genes associated with monogenic interferonopathies are also associated with systemic lupus erythematosus.
  
  
  CONCLUSIONS
  Rare genetic variants contribute to the heritability of autoimmunity and provide key insight into both novel and previously implicated immunological pathways that are disrupted in autoimmune diseases.
authors.affiliation: aRosalind Russell/Ephraim P. Engleman Rheumatology Research CenterbDepartment of Medicine, Division of Pulmonary and Critical Care, , University of California San Francisco, San Francisco, California, USA.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Chung
authors.forename: Anthony K
authors.initials: AK
authors.lastname: Shum
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics; D005090:Exodeoxyribonucleases / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000276:immunology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D010750:Phosphoproteins / Q000235:genetics
chemical_list: C508017:IL2RA protein, human; C508020:IL2RB protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D053646:Interleukin-2 Receptor beta Subunit; D010750:Phosphoproteins; D005090:Exodeoxyribonucleases; C429526:three prime repair exonuclease 1