The first deletion mutation in the TSP1-6 repeat domain of ADAMTS13 in a family with inherited thrombotic thrombocytopenic purpura
Articolo
Data di Pubblicazione:
2009
Citazione:
The first deletion mutation in the TSP1-6 repeat domain of ADAMTS13 in a family with inherited thrombotic thrombocytopenic purpura / R. Palla, S. Lavoretano, R. Lombardi, I. Garagiola, M. Karimi, A. Afrasiabi, M. Ramzi, R. De Cristofaro, F. Peyvandi. - In: HAEMATOLOGICA. - ISSN 0390-6078. - 94:2(2009 Feb), pp. 289-293.
Abstract:
The inherited deficiency of ADAMTS13 is usually associated with severe forms of thrombotic thrombocytopenic purpura. Among the mutations identified in the ADAMTS13 gene, none have been described on the TSP1-6 repeat domain. We investigated an Iranian family with a history of chronic recurrent thrombotic thrombocytopenic purpura, severe ADAMTS13 deficiency and a heterogeneous pattern of clinical symptoms among affected members. Genetic analysis revealed a homozygous deletion of nucleotides 2930-2935 (GTGCCC) in exon 23 of ADAMTS13, leading to the replacement of Cys977 by a Trp and the deletion of Ala978 and Arg979 in the TSP1-6 repeat domain. To explore the mechanism of ADAMTS13 deficiency, in vitro expression studies were performed. Western blotting, pulse-chase labeling and immunofluorescence studies demonstrated a secretion pathway defect of the mutant protein, with no intracellular accumulation. This finding is consistent with the severe ADAMTS13 deficiency but does not explain the heterogeneous clinical picture of the 3 siblings carrying the same mutation
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
ADAMTS13; Deletion; Mutation; Thrombotic thrombocytopenic purpura; TSP-1 repeat
Elenco autori:
R. Palla, S. Lavoretano, R. Lombardi, I. Garagiola, M. Karimi, A. Afrasiabi, M. Ramzi, R. De Cristofaro, F. Peyvandi
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