The novel c.774_775 ins ccgcgcc mutation combined with c.4085 T>A in the ADAMTS13 gene contributes to thrombotic thrombocytopenic purpura (TTP)

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

Toronto

Congreso; XXV ISTH Congress; 2015

ISTH

Background: PTT is a rare disease characterized by widespread intravascular platelet thrombosis.Aims: We described a case of congenital TTP with presence of a known (c.4085 T>A) and a novel (c.774_775 insccgcgcc) mutation, both in heterozygous state.Methods: The proband (P) is a male patient diagnosed TTP at the age of 37, with manifestations of thrombocytopeniaand impaired renal function. ADAMTS13 activity (normal value:40-130%), antigen (0.60-1.60μg/ml) and IgG anti-ADAMTS13 antibody (A known mutation, SNP c.-169C>T in region 5´UTR and novel mutation c.774_775ins ccgcgcc, all inheterozygous state.Father and sister: ADAMTS13 activity=46 and 56% and antigen=0.67 and 0.90μg/ml respectively; both of them IgG anti-ADAMTS13 antibody =8U/ml.Both, heterozygous for c.774_775ins ccgcgcc, presented normal ULVWF multimers. None showed ICs. In silico for thenew mutation predicted the formation of a premature stop codon during transcription (p.G258PfsX133).Conclusion: We observed (Calderazzo 2012) that c.4085A>T mutation causing ADAMTS13 intracellular retention isaccompanied by c.-169C>T in several patients (n=4). It is described that SNPs or mutations at 5?UTR region may affecttranscription and translation of proteins.The reading frame shift caused by c.774_775ins ccgcgcc also produced 133 different amino acids prior to the stop codonand has the distinctive feature of being, in turn, a doubling. Pimanda2004 and Garagiola2008 concluded that theinsertions are associated with low ADAMTS13 activity. Therefore, the compound heterozygous state would justify lowlevels of ADAMTS13 in the P.Disclosure of Interest: None DeclaredKeywords: ADAMTS13, Mutation, Thrombocytopenia, Thrombotic