A Severe Case of Congenital Thrombotic Thrombocytopenia Purpura Resulting From Compound Heterozygosity Involving a Novel ADAMTS13 Pathogenic Variant

被引：5

作者：

Conboy, Erin ^{[1
]}

Partain, Paige I. ^{[2
]}

Warad, Deepti ^{[4
]}

Kluge, Michelle L. ^{[3
]}

Arndt, Carola ^{[5
]}

Chen, Dong ^{[3
]}

Rodriguez, Vilmarie ^{[5
]}

机构：

[1] Mayo Clin, Dept Clin Genom, 200 First St SW, Rochester, MN 55905 USA

[2] Mayo Clin, Dept Pediat & Adolescent Med, 200 First St SW, Rochester, MN 55905 USA

[3] Mayo Clin, Dept Lab Med & Pathol, 200 First St SW, Rochester, MN 55905 USA

[4] Mayo Clin, Div Hematopathol, Special Coagulat Lab, 200 First St SW, Rochester, MN 55905 USA

[5] Mayo Clin, Div Pediat Hematol & Oncol, Special Coagulat Lab, 200 First St SW, Rochester, MN 55905 USA

来源：

JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY | 2018年 / 40卷 / 01期

关键词：

thrombotic thrombocytopenic purpura; TTP; congenital; mutation; pathogenic variant; ADAMTS13; Upshaw-Schulman syndrome; VON-WILLEBRAND-FACTOR; FACTOR CLEAVING PROTEASE; MUTATIONS;

D O I：

10.1097/MPH.0000000000000895

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We report a 9-year-old Chinese girl with congenital thrombotic thrombocytopenic purpura found to be a compound heterozygote for 2 pathogenic variants in the ADAMTS13 gene, including a novel variation. The girl suffered from recurrent, life-threatening episodes of thrombocytopenia and hemolysis, and laboratory testing showed ADAMST13 enzyme activity of < 5%. Sequencing of the ADAMTS13 gene revealed a previously reported missense variant, c.1787C > T (p.Ala596Val), and a novel duplication defined as c.1007_1025dup19 (p.Asp343Leufs*53); the duplication is predicted to result in a premature stop codon and protein truncation. We propose that this novel variant is partly responsible for the patient's early-onset and severe phenotype.

引用

页码：60 / 62

页数：3

共 15 条

[1] N-Acetylcysteine for Relapsing Thrombotic Thrombocytopenic Purpura: More Evidence of a Promising Drug [J].

Cabanillas, Gerardo ;

Popescu-Martinez, Andrea .

AMERICAN JOURNAL OF THERAPEUTICS, 2016, 23 (05) :E1277-E1279

[2] A phenotype-genotype correlation of ADAMTS13 mutations in congenital thrombotic thrombocytopenic purpura patients treated in the United Kingdom [J].

Camilleri, R. S. ;

Scully, M. ;

Thomas, M. ;

Mackie, I. J. ;

Liesner, R. ;

Chen, W. J. ;

Manns, K. ;

Machin, S. J. .

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2012, 10 (09) :1792-1801

[3] N-acetylcysteine reduces the size and activity of von Willebrand factor in human plasma and mice [J].

Chen, Junmei ;

Reheman, Adili ;

Gushiken, Francisca C. ;

Nolasco, Leticia ;

Fu, Xiaoyun ;

Moake, Joel L. ;

Ni, Heyu ;

Lopez, Jose A. .

JOURNAL OF CLINICAL INVESTIGATION, 2011, 121 (02) :593-603

[4] In-vitro and in-vivo consequences of mutations in the von Willebrand factor cleaving protease ADAMTSI3 in thrombotic thrombocytopenic purpura [J].

Donadelli, Roberta ;

Banterla, Federica ;

Galbusera, Miriam ;

Capoferri, Cristina ;

Bucchioni, Sara ;

Gastoldi, Sara ;

Nosari, Silvia ;

Monteferrante, Giuseppe ;

Ruggeri, Zaverio M. ;

Bresin, Elena ;

Scheiflinger, Friedrich ;

Rossi, Edoardo ;

Martinez, Constantino ;

Coppo, Rosanna ;

Remuzzi, Giuseppe ;

Noris, Marina .

THROMBOSIS AND HAEMOSTASIS, 2006, 96 (04) :454-464

[5] Natural history of Upshaw-Schulman syndrome based on ADAMTS13 gene analysis in Japan [J].

Fujimura, Y. ;

Matsumoto, M. ;

Isonishi, A. ;

Yagi, H. ;

Kokame, K. ;

Soejima, K. ;

Murata, M. ;

Miyata, T. .

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2011, 9 :283-301

[6]

George JN, 2014, NEW ENGL J MED, V371, P1847, DOI [10.1056/NEJMra1312353, 10.1056/NEJMc1410951]

[7] Molecular characterization of four ADAMTS13 mutations responsible for congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome) [J].

Hommais, Antoine ;

Rayes, Julie ;

Houllier, Anne ;

Obert, Bernadette ;

Legendre, Paulette ;

Veyradier, Agnes ;

Girma, Jean-Pierre ;

Ribba, Anne-Sophie .

THROMBOSIS AND HAEMOSTASIS, 2007, 98 (03) :593-599

[8] Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura [J].

Levy, GG ;

Nichols, WC ;

Lian, EC ;

Foroud, T ;

McClintick, JN ;

McGee, BM ;

Yang, AY ;

Siemieniak, DR ;

Stark, KR ;

Gruppo, R ;

Sarode, R ;

Shurin, SB ;

Chandrasekaran, V ;

Stabler, SP ;

Sabio, H ;

Bouhassira, EE ;

Upshaw, JD ;

Ginsburg, D ;

Tsai, HM .

NATURE, 2001, 413 (6855) :488-494

[9] Treatment of refractory thrombotic thrombocytopenic purpura with N-acetylcysteine: a case report [J].

Li, Gloria W. ;

Rambally, Siayareh ;

Kamboj, Jasmine ;

Reilly, Sean ;

Moake, Joel L. ;

Udden, Mark M. ;

Mims, Martha P. .

TRANSFUSION, 2014, 54 (05) :1221-1224

[10] Two novel ADAMTS13 gene mutations in thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome (TTP/HUS) [J].

Licht, C ;

Stapenhorst, L ;

Simon, T ;

Budde, U ;

Schneppenheim, R ;

Hoppe, B .

KIDNEY INTERNATIONAL, 2004, 66 (03) :955-958

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