Several polymorphisms (SNP) in the ADAMTS13 gene in thrombotic thrombocytopenic purpura (TTP)

CALDERAZZO JC; KEMPFER AC; PAIVA J; SANCHEZ LUCEROS A; WOODS AI; LAZZARI MA

Nice

Congreso; 22nd International Congress on Thrombosis; 2012

Liga del Mediterraneo

BackgroundTTP is a disease characterized by microvascular thrombosis, often associated with deficiency of ADAMTS13 activity. Over 77 ADAMTS13 mutations that have been reported, most of which are located at the N-terminus of ADAMTS13, indicating the importance of these domains. Donadelli (2006) found several polymorphisms (SNPs) within exons and introns limits in patients in which mutations have not been identified and suggested that these SNPs would influence ADAMTS13 functional abnormalities.We report a case of a fourteen-year-old (y) boy, where the plasma multimeric analysis of VWF (33% of ultralarge multimers, ULVWF) in addition to the clinical pattern, allowed us the TTP diagnosis.MethodsADAMTS13 activity (normal values=40-130%) was evaluated by chromogenic VWF-73 ELISA kit, IgG anti-ADAMTS13 antibodies (positive samples>15 U/ml) and ULVWF multimers (normal valueT), C19T, G354A, C582T, 686+4 T>G, C1342G, C1852G, in homozygosity state and 3045-41 G>A, 3045?48 T>C, G3108A in heterozygosity state. In addition, it was identified a novel mutation/SNP T3718G in exon 27 and a single-nucleotide guanine deletion (4050delG) in exon 28, both in heterozygosis. The patient´s mother had 51% of ADAMTS13 activity and lack of ULVWF. DNA sequencing identified all the SNPs but in heterozygosity state. Also, it was identified the same deletion in exon 28, but the mutation/SNP in exon 27 was not detected.CommentPlaimauer (2006) observed in the in vitro expression that SNP C1852G led to a reduced secretion (27%) and an ADAMTS13 activity of 14%, and that the combination of SNPs C19T, C1342G and C1852G also caused a decrease in its activity (32%). The deletion present in exon 28 (heterozygous) in the patient and in the mother seems not be enough, by itself, to cause severe impairment on the activity.The evaluation of the potential role of the SNPs alone or in combination (homozygous), the new SNP/mutation in exon 27 or the deletion in exon 28 combined with SNPs in the development of ADAMTS13 deficiency, should be a starting point in the analysis of the ADAMTS13 gene in the patient.