ArticleThe New England journal of medicine2014
Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy.
Article in The New England journal of medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 298 papers, 3 of them syntheses that pooled it.
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Who cites it
298 citing papers in PubMed, 3 syntheses or guidelines pooled it, 692 citations in OpenAlex.
- A wide spectrum of phenotype of deficiency of deaminase 2 (DADA2): a systematic literature review.Orphanet journal of rare diseases · 2023Pooled it
- 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Polyarteritis Nodosa.Arthritis care & research · 2021Guideline
- 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Polyarteritis Nodosa.Arthritis & rheumatology (Hoboken, N.J.) · 2021Guideline
- Clinical presentations and long term prognosis of childhood onset polyarteritis nodosa in single centre of Korea.Scientific reports · 2021Trial
- Advancements in Diagnosis and Care for Immune Dysregulation and Inborn Errors of Immunity in Pediatric Rheumatology: Our 50-Year Journey.Arthritis care & research · 2026Review
- Adenosine deaminase type 2 deficiency: From rare to common.Journal of human immunity · 2026Review
- ADA2 genotype and enzyme activity may predict vasculitic or hematologic DADA2 phenotype.Journal of human immunity · 2026Article
- When to consider an inborn error of immunity: clues for physicians.Internal medicine journal · 2026Review
- Cutaneous Pediatric Vasculitis: A Clinico-Histopathological Overview of Common and Novel Entities.Dermatopathology (Basel, Switzerland) · 2026Review
- DADA2 as a Model of Monogenic Immune Vasculopathy: From Immunopathogenesis to Precision Therapeutics.Biomolecules · 2026Review
- Decoding variants of uncertain significance in systemic autoinflammatory diseases.Nature reviews. Rheumatology · 2026Review
- Sneddon syndrome: one phenotype, distinct pathophysiological entities with tailored treatments.Science China. Life sciences · 2026Article
- Monogenic autoimmune and autoinflammatory disorders in adulthood: recent discoveries and implications for rheumatology practice.Rheumatology (Oxford, England) · 2026Review
- Aneurysmal Subarachnoid Hemorrhage in Pediatric DADA2: A Case Report and Literature Review.Cureus · 2026Article
- ADA2-deficient cells exhibit increased levels of cell death and metabolic disturbances.Cell death discovery · 2026Article
- Diagnostic Implications and Correlates of Plasma Adenosine Deaminase 2 Activity and ADA2 Variants.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Hepatic Vascular Involvement in Adenosine Deaminase 2 Deficiency (DADA2): Case Reports and Literature Review.Diagnostics (Basel, Switzerland) · 2026Article
- A Review of Adenosine Deaminase 2 (ADA2) as a Biomarker of Monocyte/Macrophage Activation.Current allergy and asthma reports · 2026Review
- Current and future advances in practice: polyarteritis nodosa and related vasculitides.Rheumatology advances in practice · 2026Review
- Decoding neurovascular signatures: advanced imaging insights in DADA2-Related Cerebral Microangiopathy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
238 more citing papers are in PubMed but not listed here.
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Authors and funding
35 authors at 16 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPolyarteritis nodosa is a systemic necrotizing vasculitis with a pathogenesis that is poorly understood. We identified six families with multiple cases of systemic and cutaneous polyarteritis nodosa, consistent with autosomal recessive inheritance. In most cases, onset of the disease occurred during childhood.
methodsWe carried out exome sequencing in persons from multiply affected families of Georgian Jewish or German ancestry. We performed targeted sequencing in additional family members and in unrelated affected persons, 3 of Georgian Jewish ancestry and 14 of Turkish ancestry. Mutations were assessed by testing their effect on enzymatic activity in serum specimens from patients, analysis of protein structure, expression in mammalian cells, and biophysical analysis of purified protein.
resultsIn all the families, vasculitis was caused by recessive mutations in CECR1, the gene encoding adenosine deaminase 2 (ADA2). All the Georgian Jewish patients were homozygous for a mutation encoding a Gly47Arg substitution, the German patients were compound heterozygous for Arg169Gln and Pro251Leu mutations, and one Turkish patient was compound heterozygous for Gly47Val and Trp264Ser mutations. In the endogamous Georgian Jewish population, the Gly47Arg carrier frequency was 0.102, which is consistent with the high prevalence of disease. The other mutations either were found in only one family member or patient or were extremely rare. ADA2 activity was significantly reduced in serum specimens from patients. Expression in human embryonic kidney 293T cells revealed low amounts of mutant secreted protein.
conclusionsRecessive loss-of-function mutations of ADA2, a growth factor that is the major extracellular adenosine deaminase, can cause polyarteritis nodosa vasculopathy with highly varied clinical expression. (Funded by the Shaare Zedek Medical Center and others.).
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