Analysis of AGBl3 mutations in patients with hypocomplementemic urticarial vasculitis syndrome

Hypocomplementemic Urticarial Vasculitis Syndrome (HUVS), a rare autoimmune disease, is characterized by complement deficiency and the presence of C1q antibody in serum. Less than 200 cases have been reported in the literature for extremely rare HUVS. While this disease is more common in women than in men, it is rarely seen in children. The pathophysiology and genetic etiology of HUVS, which is characterized by low complement levels, anti-C1q precipitates in serum and accompanying fever, weakness, fatigue, muscle rheumatism, recurrent urticaria, have not been fully elucidated. AGBL3 was determined as a candidate gene in whole exome sequencing studies we conducted in a trio family with a child with HUVS. AGBL3 protein is involved in post-translational modifications of tubulins and forms ∆2-tubulin. It has been reported that Tubulins associated with autoinflammatory and autoimmune diseases. This suggests that AGBL3 may be associated with inflammation through microtubules. In "whole exome sequencing" study, the c.769.C> T mutation in AGBL3 gene was homozygous in the child with HUVS, and heterozygous in the father with mucocutous Behçet's and healthy mother. In this thesis, AGBL3 gene exon regions are examined by Sanger sequencing method in 2 HUVS patients. As a result of sequencing, variations were found in different introns and exons regions in patients. In addition, estimates have been made using various bioinformatics tools for p.Gln257Ter protein change caused by mutation in c.769.C>T region. The results show that genetic etiology of HUVS is heterogeneous and AGBL3 gene mutations may be related to HUVS. Key Words: HUVS, AGBL3, CCP3, AGBL3 Mutation, Urticarial Vasculitis The present work was supported by the Research Fund of Istanbul University. Project No. 36201