What are the genetic features of polyarteritis nodosa (PAN)?

Updated: Nov 14, 2017
  • Author: Dana Jacobs-Kosmin, MD, FACP; Chief Editor: Herbert S Diamond, MD  more...
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Answer

Loss-of-function mutations in CECR1 (alsoknown as ADA2), the gene that encodes adenosine deaminase 2 (ADA2), have been associated with a spectrum of vascular and inflammatory phenotypes that includes polyarteritis nodosa. [13]  Navon Elkan and colleagues identified six families with multiple cases of systemic and cutaneous polyarteritis nodosa, most of which had onset during childhood. In all the families, disease was traced to recessive mutations in CECR1 that resulted in reduced activity of ADA2. [14]

Possible roles of ADA2 include regulation of the proliferation of activated T cells and macrophages and the differentiation of monocytes to macrophages. Reduction in ADA2 activity  may affect the adenosine inflammatory-response pathway. [14]

Similarly, Gonzalez Santiago et al report two siblings with novel compound heterozygous mutations in CECR1 who were diagnosed with cutaneous PAN in early childhood. [15]

In a study of patients with early-onset livedo reticularis and/or hemorrhagic/ischemic strokes in the context of inflammation or PAN, Caorsi et al detected biallelic homozygous or compound heterozygous CECR1 mutations in 15 of 48 patients from 43 families. In patients with CECR1 mutations, the mean age of onset of disease was 24 months (6 months to 7 years). [16]


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