title: Dermatologic Features of ADA2 Deficiency in Cutaneous Polyarteritis Nodosa.
abstract: OBJECTIVE
  Mutations in the CERC1 gene associated with deficiency in the ADA2 protein (DADA2) have been implicated in the pathogenesis of cutaneous polyarteritis nodosa (cPAN) and early-onset vasculopathy. DADA2 is not only limited to cPAN and vasculopathy but also includes immunodeficiency that affects several cellular compartments, including B cells; however, some patients appear to have a more indolent, skin-limited disease.
  
  
  METHODS
  In this report, we describe 2 white siblings (female and male) with a history of cPAN with DADA2 as a result of novel compound heterozygous mutations inherited in trans in the CECR1 gene (c.37_39del [p.K13del] and c.1159C>A [p.N328K]). The onset of disease was earlier in the female sibling than the male sibling although both were diagnosed as having cPAN in early childhood. The disease is associated with a more significant immunodeficiency and other systemic symptoms in the female than the male sibling.
  
  
  CONCLUSIONS
  These findings suggest a genetic cause of cPAN in some patients. Therefore, DADA2 should be considered in patients with cPAN, specifically in those whose conditions are diagnosed at an early age, regardless of their ethnicity, presence or absence of systemic symptoms, or a family history of the disease.
authors.affiliation: Department of Dermatology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Tania M
authors.initials: TM
authors.lastname: Gonzalez Santiago
authors.affiliation: Turku Center for Biotechnology, University of Turku, Turku, Finland.
authors.forename: Andrey
authors.initials: A
authors.lastname: Zavialov
authors.affiliation: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki.
authors.forename: Janna
authors.initials: J
authors.lastname: Saarela
authors.affiliation: Immunodeficiency Unit, Inflammation Center, Helsinki University, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Seppanen
authors.affiliation: Rheumatology Division, Department of Internal Medicine and Pediatrics, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Reed
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Roshini S
authors.initials: RS
authors.lastname: Abraham
authors.affiliation: Department of Dermatology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Gibson
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics*; D000293:Adolescent; D002648:Child; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation; D010488:Polyarteritis Nodosa / Q000235:genetics / Q000473:pathology*; D035781:Siblings; D012871:Skin Diseases / Q000235:genetics / Q000473:pathology*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C408373:ADA2 protein, human; D000243:Adenosine Deaminase