Congenital thrombotic thrombocytopenic purpura (Upshaw–Schulman syndrome) caused by novel <i><scp>ADAMTS</scp>13</i> mutations

Kim, Sujeong; Lee, Ki-O; Yoo, Keon Hee; Kim, Sun‐Hee; Oh, Doyeun; Kim, Hee‐Jin

doi:10.1111/bjh.13564

Cited by 4 publications

(2 citation statements)

References 10 publications

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“…Indeed, more recent studies have shown that the C-terminal ADAMTS13 fragments display antithrombotic activity, and that this activity is mediated, independently of proteolytic activity, by disulfide-bond-reducing activity localized to the C-terminal TSP1 2-8 and CUB domains of ADAMTS13 [24,25]. Our case report, together with other previously reported mutations in the distal TSP-1 and CUB domains that result in clinically overt cTTP [26][27][28][29][30], highlight the important physiological role played by these domains in ADAMTS13-mediated cleavage of VWF.…”

Section: Discussionsupporting

confidence: 76%

Untitled

2022

RRHOAJ

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Thrombotic thrombocytopenic purpura (TTP) is a life-threatening form of thrombotic microangiopathy (TMA) characterized by recurrent episodes of thrombocytopenia and microangiopathic hemolytic anemia (MAHA), sometimes associated with ischemic damage of the brain and kidneys. Congenital TTP (cTTP), also known as Upshaw-Schulman syndrome, is a rare disease caused by compound heterozygous, or more rarely, homozygous mutations in the gene encoding the von Willebrand factor (VWF) cleaving protease, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). The disease course in cTTP is variable and genotype-phenotype correlations are complex. In this report we describe a case of cTTP in a patient from Saudi Arabia caused by a novel homozygous mutation (c.2882delC; p. Cys962Alafs*3) predicted to result in truncation of a third of the C-terminal region of the ADAMTS13 protein, including the distal TSP-1 and CUB domains. The cTTP in our patient was characterized by severe ADAMTS13 deficiency (<2%), early onset (severe neonatal hyperbilirubinemia) recurrent episodes of thrombocytopenia and MAHA, requiring prophylactic treatment with fresh frozen plasma infusions. No neurological or renal manifestations were present. This case report provides further evidence that both the distal TSP-1 and CUB domains are essential for the VWF-cleaving activity of ADAMTS13

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Section: Discussionsupporting

confidence: 76%

Untitled

2022

RRHOAJ

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“…24,25 . Our case report, together with other previously reported mutations in the distal TSP-1 and CUB domains that result in clinically overt cTTP, [26][27][28][29][30] highlight the important physiological role played by these domains in ADAMTS13-mediated cleavage of VWF.…”

Section: Discussionsupporting

confidence: 70%

Congenital thrombotic thrombocytopenic purpura due to a novel homozygous mutation in the ADAMTS13 gene: a case report

Yousef Almadani,

Abdulbasit Almelibar I,

I Elhefnawy

et al. 2022

HTIJ

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Thrombotic thrombocytopenic purpura (TTP) is a life-threatening form of thrombotic microangiopathy (TMA) characterized by recurrent episodes of thrombocytopenia and microangiopathic hemolytic anemia (MAHA), sometimes associated with ischemic damage of the brain and kidneys. Congenital TTP (cTTP), also known as Upshaw–Schulman syndrome, is a rare disease caused by compound heterozygous, or more rarely, homozygous mutations in the gene encoding the von Willebrand factor (VWF) cleaving protease, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). The disease course in cTTP is variable and genotype-phenotype correlations are complex. In this report we describe a case of cTTP in a patient from Saudi Arabia caused by a novel homozygous mutation (c.2882delC; p.Cys962Alafs*3) predicted to result in truncation of a third of the C-terminal region of the ADAMTS13 protein, including the distal TSP-1 and CUB domains. The cTTP in our patient was characterized by severe ADAMTS13 deficiency (<2%), early onset (severe neonatal hyperbilirubinemia) recurrent episodes of thrombocytopenia and MAHA, requiring prophylactic treatment with fresh frozen plasma infusions. No neurological or renal manifestations were present. This case report provides further evidence that both the distal TSP-1 and CUB domains are essential for the VWF-cleaving activity of ADAMTS13.

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ADAMTS13: more than a regulator of thrombosis

Feng

et al. 2016

Int J Hematol

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ADAMTS13, a plasma reprolysin-like metalloprotease, proteolyzes von Willebrand factor (VWF). ADAMTS13 is primarily synthesized by hepatic stellate cells (HSCs), and mainly regulates thrombogenesis by cleaving VWF. Recent studies demonstrate that ADAMTS13 also plays a role in the down-regulation of inflammation, regulation angiogenesis, and degradation of extracellular matrix. The purpose of this review is to introduce the state of progress with respect to some of the theorized roles of ADAMTS13.

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Congenital thrombotic thrombocytopenic purpura (Upshaw–Schulman syndrome) caused by novel ADAMTS13 mutations

Abstract: . (2003) Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor.

Cited by 4 publications

References 10 publications

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Congenital thrombotic thrombocytopenic purpura due to a novel homozygous mutation in the ADAMTS13 gene: a case report

ADAMTS13: more than a regulator of thrombosis

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