title: Deficiency of Adenosine Deaminase 2 Causes Antibody Deficiency.
abstract: OBJECTIVE
  Determining the monogenic cause of antibody deficiency and immune dysregulation in a non-consanguineous family with healthy parents, two affected children, and one unaffected child.
  
  
  METHODS
  Whole Exome Sequencing (WES) was performed in the index family. WES results were confirmed by Sanger Sequencing. Dried plasma spots of the male patient and his mother were analyzed for ADA2 enzymatic activity.
  
  
  RESULTS
  Following data analysis of WES, we found a compound heterozygous mutation in CECR1 (encoding adenosine deaminase 2, ADA2) that segregated in the two affected children. Enzyme activity measurement confirmed a severely diminished ADA2 activity in our patient. The 32 year old index patient was suffering from recurrent respiratory infections and was previously diagnosed with common variable immunodeficiency (CVID), showing no signs of vasculitis. His sister had a systemic lupus erythematosus (SLE)-like phenotype and died at age 17.
  
  
  CONCLUSIONS
  Deficiency of ADA2 (DADA2) has been reported to cause vasculopathy and early-onset stroke. Our case suggests that it should also be considered when evaluating patients with antibody deficiencies and immune dysregulation syndromes.
authors.affiliation: CCI-Center for Chronic Immunodeficiency, Universitätsklinikum Freiburg, Engesserstraße 4, 79108, Freiburg, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Schepp
authors.affiliation: CCI-Center for Chronic Immunodeficiency, Universitätsklinikum Freiburg, Engesserstraße 4, 79108, Freiburg, Germany.
authors.forename: Alla
authors.initials: A
authors.lastname: Bulashevska
authors.affiliation: Zentrum für Kinder- und Jugendmedizin, Universitätsmedizin Mainz, 55131, Czernyweg, Mainz, Germany.
authors.forename: Wilma
authors.initials: W
authors.lastname: Mannhardt-Laakmann
authors.affiliation: Science and Technology Department, BGI-Shenzhen, Main Building, Beishan Industrial Zone, Yantian District, Shenzhen, 518083, China.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Cao
authors.affiliation: Science and Technology Department, BGI-Shenzhen, Main Building, Beishan Industrial Zone, Yantian District, Shenzhen, 518083, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.affiliation: CCI-Center for Chronic Immunodeficiency, Universitätsklinikum Freiburg, Engesserstraße 4, 79108, Freiburg, Germany.|Institut für klinische Pathologie, Universitätsklinikum Freiburg, Breisacher Str. 115A, 79106, Freiburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Seidl
authors.affiliation: Duke Biochemistry, University of Duke, Nanaline H. Duke, Box 3711, DUMC, Durham, NC, 27710, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Kelly
authors.affiliation: Duke Biochemistry, University of Duke, Nanaline H. Duke, Box 3711, DUMC, Durham, NC, 27710, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Hershfield
authors.affiliation: CCI-Center for Chronic Immunodeficiency, Universitätsklinikum Freiburg, Engesserstraße 4, 79108, Freiburg, Germany. bodo.grimbacher@uniklinik-freiburg.de.|Institute of Immunology and Transplantation, Royal Free Hospital, University College London, Pond Street, London, NW3 2QG, UK. bodo.grimbacher@uniklinik-freiburg.de.
authors.forename: Bodo
authors.initials: B
authors.lastname: Grimbacher
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D002648:Child; D017074:Common Variable Immunodeficiency / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D059788:Dried Blood Spot Testing; D059472:Exome; D005260:Female; D015870:Gene Expression; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000235:genetics*; D007074:Immunoglobulin G / Q000097:blood / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000473:pathology; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D036341:Intercellular Signaling Peptides and Proteins; C408373:ADA2 protein, human; D000243:Adenosine Deaminase
keywords: Deficiency of ADA2; antibody deficiency; common variable immunodeficiency; primary immunodeficiency; recurrent infections; systemic lupus erythematosus