ADA2 Mutation: A Genetic Basis for Polyarteritis Nodosa

Recessive loss-of-function mutations affecting growth factor ADA2 can cause polyarteritis nodosa vasculopathy with variable clinical expression.

Polyarteritis nodosa (PAN) is a small-to-medium-sized arteritis that causes manifestations of tissue ischemia, such as Raynaud phenomenon and digital necrosis, with potentially fatal involvement of internal vessels. Autosomal recessive familial PAN manifests early in life and includes both cutaneous and systemic involvement.

Nineteen Georgian Jewish patients with familial PAN were evaluated, 10 of whom were diagnosed before age 10 years. Exome sequencing in 16 patients revealed the Gly47Arg substitution in the CECR1 gene, which encodes adenosine deaminase 2 (ADA2). In other cohorts, compound heterozygosity for Arg169Gln and Pro251Leu or Gly47Val and Trp264Ser was identified. Expression of these mutants in cells resulted in lower amounts of e…

Reviewing Author

Hensin Tsao, MD, PhD

Disclosures

Consultant / advisory board Lubax; WorldCare Clinical

EquityLubax

Grant / Research support NIH; Department of Defense; American Skin Association; Piramal

Editorial boardsBritish Journal of Dermatology; Journal of the American Academy of Dermatology; Journal of Investigative Dermatology

Leadership positions in professional societies American Academy of Dermatology (Chair, Skin Cancer and Melanoma Committee); American Board of Dermatology (Director)