OR13-002 Recessive mutations in CECR1, encoding adenosine deaminase 2 (ADA2), cause systemic and cutaneous polyarteritis nodosa (PAN)

Ephrat Levy‐Lahad ,P Elkan-Navon,Ef Emirogullari,Yair Anikster ,Abraham Zlotogorski ,Reeval Segel ,Pj Hashkes ,Sb Pierce ,L Harel ,Dina Marek‐Yagel ,A Rubinow ,Pf Renbaum ,Fatoş Yalçınkaya ,Özgür Kasapçopur ,Jj Press ,Sharon Zeligson ,Shai Padeh ,Judith Barash ,Amihood Singer ,Yy Berkun ,Elon Pras ,Mustafa Tekin ,M Shohat ,Tomas Walsh ,Klevit Re ,Ariella Weinberg‐Shukron ,M Mukamel ,Mk Lee ,M-C King

doi:10.1186/1546-0096-11-s1-a264

Abstract

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of middle-sized arteries, found in both adults and children. Disease pathogenesis is poorly understood. We identified multiple cases of systemic PAN and cutaneous PAN in families and individuals of Georgian-Jewish ancestry, consistent with autosomal recessive inheritance. While most cases (17/20) had childhood onset, cutaneous PAN could also initiate in middle age.

Highlights

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of middle-sized arteries, found in both adults and children
We identified multiple cases of systemic PAN and cutaneous PAN in families and individuals of Georgian-Jewish ancestry, consistent with autosomal recessive inheritance
While most cases (17/20) had childhood onset, cutaneous PAN could initiate in middle age

Summary

Introduction

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of middle-sized arteries, found in both adults and children. We identified multiple cases of systemic PAN and cutaneous PAN in families and individuals of Georgian-Jewish ancestry, consistent with autosomal recessive inheritance. While most cases (17/20) had childhood onset, cutaneous PAN could initiate in middle age. Turkish patient was compound heterozygous for G47V and W264S. In the Georgian-Jewish population, the frequency of G47R was 0.05, reflecting the high prevalence of PAN in this endogamous community. The other mutations were absent from ethnically matched controls. ADA2 activity was significantly reduced in patient sera. Expression of mutant proteins in HEK293T cells yielded significantly reduced levels of secreted ADA2 and biophysical assays indicated reduced protein stability

Methods

Results

Conclusion