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.
References
Jun 1, 1985·Cell·M BoshartW Schaffner
Oct 5, 2001·Nature·G G LevyH M Tsai
Nov 1, 2001·Best Practice & Research. Clinical Haematology·M Furlan, B Lämmle
Oct 23, 2002·The Journal of Cell Biology·Kemin TanJia-huai Wang
Jan 17, 2004·Seminars in Hematology·Koichi Kokame, Toshiyuki Miyata
Mar 11, 2004·Journal of Thrombosis and Haemostasis : JTH·A VeyradierJ-P Girma
May 12, 2004·The Journal of Biological Chemistry·Fumiaki BannoToshiyuki Miyata
Sep 16, 2004·Blood·Jan-Dirk StudtBernhard Lämmle
Nov 4, 2004·British Journal of Haematology·Flora PeyvandiPier Mannuccio Mannucci
Apr 13, 2005·The Journal of Biological Chemistry·Elaine M MajerusJ Evan Sadler
Sep 15, 2005·Blood·Barbara PlaimauerFriedrich Scheiflinger
Jan 3, 2006·Seminars in Thrombosis and Hemostasis·Suresh G ShelatX Long Zheng
Feb 2, 2006·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Yugo ShibagakiToshiro Fujita
Feb 3, 2006·Human Mutation·Flora PeyvandiPier Mannuccio Mannucci
Jun 27, 2006·Journal of Thrombosis and Haemostasis : JTH·Z TaoJ-F Dong
Jun 30, 2006·Thrombosis and Haemostasis·Reinhard SchneppenheimBernhard Lämmle
Sep 28, 2006·Thrombosis and Haemostasis·Roberta DonadelliUNKNOWN International Registry of Recurrent and Familial HUS/TTP
May 26, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Karl C Desch, David G Motto
Sep 13, 2007·Thrombosis and Haemostasis·Antoine HommaisAnne-Sophie Ribba
Nov 9, 2007·Journal of Thrombosis and Haemostasis : JTH·K KokameT Miyata
Nov 23, 2007·Journal of Thrombosis and Haemostasis : JTH·R S CamilleriS J Machin
Jan 29, 2008·Haematologica·Flora PeyvandiPier Mannuccio Mannucci
Jun 25, 2008·Blood·J Evan Sadler
Citations
Jan 9, 2010·International Journal of Hematology·Han-Mou Tsai
Feb 3, 2009·Haematologica·Miriam GalbuseraGiuseppe Remuzzi
Sep 23, 2014·Thrombosis Research·Almudena Pérez-RodríguezMaría Fernanda López-Fernández
Jul 25, 2014·Thrombosis and Haemostasis·Almudena Pérez-RodríguezMaría Fernanda López-Fernández
Oct 12, 2013·Pediatric Blood & Cancer·Ayse MetinAytemiz Gurgey
Oct 23, 2009·Human Mutation·Luca A LottaFlora Peyvandi
Jan 8, 2014·Thrombosis Research·Marzia MenegattiFlora Peyvandi
Apr 25, 2012·Blood·Luca A LottaFlora Peyvandi
Jan 16, 2010·Blood·Sheng-Yu JinX Long Zheng
Aug 5, 2010·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Luis Fernando BittarJoyce M Annichino-Bizzacchi
Sep 6, 2015·Clinical Journal of the American Society of Nephrology : CJASN·Erica RuraliMarina Noris