Congenital thrombotic thrombocytopenic purpura (TTP) caused by compound heterozygosity of c.1225C>T and a novel c.2321delG ADAMTS13 gene mutations

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

Toronto

Congreso; ISTH; 2015

ISTH

ISTH 2015 Abstract SubmissionTopic: ADAMTS13ISTH15ABS-2854CONGENITAL THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP) CAUSED BY COMPOUNDHETEROZYGOSITY OF C.1225C>T AND A NOVEL C.2321DELG ADAMTS13 GENE MUTATIONSAna C. Kempfer1, Juvenal Paiva* 2, Adriana I. Woods1, Analía Sanchez-Luceros1, 2, María A. Lazzari11Laboratorio de Hemostasia y Trombosis, IMEX-CONICET, Academia Nacional de Medicina, 2Hemostasia y Trombosis,Instituto De Investigaciones Hematológicas, Academia Nacional De Medicina, Ciudad Autónoma de Buenos Aires,ArgentinaPreferred Presentation Method: Poster onlyTravel Grant Application: Reach the WorldI confirm fulfilling the criteria for the Reach the World Award: YesCountry of origin: ArgentinaBackground: Severe deficiency of ADAMTS13 may result in von Willebrand factor ultralarge multimers (ULVWF)spontaneously interacts with platelet receptors, resulting in recurrent attacks of microvascular thrombosis.Aims: We hypothesized that a compound heterozygous for both a known mutation (c.1225C>T) and a novel mutation(c.2321delG) may confer a more severe TTP phenotype.Methods: Patient (P) presenting purpura and jaundice, with hemolytic anemia, thrombocytopenia and reticulocytosis atbirth followed by several episodes during her first year of life. ADAMTS13 activity (normal value=40-130%), antigen (0.60-1.60μg/ml), and IgG anti-ADAMTS13 antibody (T inherited from the father and a novel mutation c.2321delGinherited from the mother.Conclusion: The c.1225C>T (p.R409W) mutation affects the TPS1domain, abolishing ADAMTS13 secretion. In a familywith P in homozygous state to this mutation found by Camilleri 2012, the parents, in heterozygous state, showed normalactivity and subnormal levels of antigen, like our P?s father. On the other hand, in silico tools predicted the novel mutationc.2321delG (p.G774AfsX3) produced the reading frameshift with formation of a premature stop codon which would resultin a nonfunctional protein.We conclude that the genotype of P, due to compound heterozygosity of two mutations, would produce the TTPphenotype.Disclosure of Interest: None DeclaredKeywords: ADAMTS13, Genotype, Phenotype, Thrombotic thrombocytopenic purpura