Mutation Spectrum of ADAMTS13 Gene in Patients with Upshaw-Schulman Syndrome (USS) in Russia

Upshaw-Schulman syndrome (USS) is a rare inherited autosomal recessive thrombotic microangiopathy affecting less than 1/1,000,000 individuals. It is a congenital form of thrombotic thrombocytopenic purpura (TTP) caused by ADAMTS13 protease deficiency because of mutations in the ADAMTS13 gene. USS is characterized by the formation of platelet thrombi in the microcirculation, accompanied by hemolytic anemia, thrombocytopenia, and clinical and laboratory signs of renal and neurological failure. The aim of this study was to describe the ADAMTS13 gene mutation spectrum in the Russian population. We analyzed the ADAMTS13 gene in 45 unrelated patients with TTP of unknown origin. DNA was extracted from blood cells using the phenol-chlorophorm method, and all exons of the gene were investigated using Sanger sequencing. In 15 out of 45 patients, we identified 20 different variants associated with USS, including two frameshift, two variants affecting the splice site, one nonsense and fifteen missense mutations. Eight out of those mutations were previously undescribed. Tree variants were revealed more than once: p.Arg1060Trp (7 patients), p.Glu1326ArgfsTer6 (7 patients) and p.Cys1067SerfsTer30 (3 patients). Variants (p.Arg1060Trp) and p.Glu1326ArgfsTer6 prevailed in the global population; however, p.Cys1067SerfsTer30 was not previously described in the European population. Our results expand the existing knowledge of the molecular basis of USS and may contribute to improved genetic diagnostics in Russia.