Late onset thrombosis in two Japanese patients with compound heterozygote protein S deficiency

Taniguchi, Fumina; Morishita, Eriko; Sekiya, Akiko; Yamaguchi, Daisuke; Nomoto, Haruka; Kobayashi, Erina; Takata, Mao; Kosugi, Ikuko; Takeuchi, Nobuyasu; Asakura, Hitoshi; Ohtake, Shigeki

doi:10.1016/j.thromres.2015.03.023

Cited by 6 publications

(3 citation statements)

References 9 publications

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“…Homozygous or compound heterozygous PS deficiency is extremely rare, usually presenting with massive VTE or purpura fulminans neonatally 1 25. In the recent 20 years, several reports of compound heterozygosity with later onset of VTE were also available in the literature 22 26–29. The probands in these studies remained free of thrombosis until they became teenagers and suffered from recurrent thrombosis after that, which was the same as the propositus reported in our own study.…”

Section: Discussionsupporting

confidence: 76%

Compound heterozygous mutations identified in severe type I protein S deficiency impaired the secretion of protein S

Zhou

Shen

et al. 2019

J Clin Pathol

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AimsHereditary protein S (PS) deficiency is one of the natural anticoagulant deficiencies causing thrombophilia. We herein described a young male with recurrent deep venous thrombosis, who was diagnosed as type I PS deficiency with compound heterozygous mutations of PROS1 gene. We aimed to analyse the relationship between the genotype and phenotype detection and investigate the pathological mechanisms of PROS1 mutations causing PS deficiency.MethodsGenetic analysis of PROS1 gene was carried out by direct sequencing. Thrombin generation potential and the inhibition function of thrombin generation by plasma PS were detected by thrombin generation test (TGT). The mRNA transcription level of mutant PS in vitro was measured by real-time PCR, while the protein level was evaluated by western blot and ELISA. Cellular distribution of the protein was further analysed by immunofluorescence.ResultsCompound heterozygous mutations (PROS1 c.1551_1552delinsG, p.Thr518Argfs*39 and PROS1 c.1681C>T, p.Arg561Trp) were identified in the propositus, and the former one was a novel small indel mutation. TGT results showed impaired inhibition of thrombin generation with the addition of activated protein C in his parents with certain heterozygous mutations. In vitro expression study, p.Thr518Argfs*39 mutant produced truncated protein retained in the cytoplasm, while p.Arg561Trp mutant partially affected the secretion of PS. Both mutations are located in C-terminal sex hormone-binding globulin (SHBG)-like domain of PS.ConclusionsCompound heterozygous mutations identified in the study have strong detrimental effect, causing severe type I PS deficiency in the propositus. SHBG-like domain of PS might play an important role in PS secretion system.

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Section: Discussionsupporting

confidence: 76%

Compound heterozygous mutations identified in severe type I protein S deficiency impaired the secretion of protein S

Zhou

Shen

et al. 2019

J Clin Pathol

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“…Given that TMA or TTP complicated with PS deficiency does not seem to have been reported previously, it would be important to understand the impact of heterozygous PS deficiency on TMA. Compound heterozygote PS deficiency generally results in neonatal purpura fulminans or severe thrombosis in early childhood . Additionally, 28 out of 173 patients with the genetic defect in PROS‐1 (protein S (alpha)) had late‐onset deep vein thrombosis .…”

Section: Discussioncontrasting

confidence: 65%

“…Compound heterozygote PS deficiency generally results in neonatal purpura fulminans or severe thrombosis in early childhood. 10 Additionally, 28 out of 173 patients with the genetic defect in PROS-1 (protein S (alpha)) had late-onset deep vein thrombosis. 11 PS deficiency is associated with recurrent deep venous thrombosis, and appears to mediate arterial as well as venous thrombosis in some juvenile patients.…”

Section: Discussionmentioning

confidence: 99%

Influenza‐associated thrombotic microangiopathy with unbalanced von Willebrand factor and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 levels in a heterozygous protein S‐deficient boy

Tsujii

Nogami

Yoshizawa

et al. 2016

Pediatrics International

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Influenza infections often cause pneumonia, but there is limited information on thrombotic microangiopathy (TMA) in these circumstances. We report the case of an 11-year-old boy who developed TMA during the acute phase of H1N1 influenza. Plasma von Willebrand factor (VWF) was elevated, whereas a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activity was mildly reduced in the absence of ADAMTS13-neutralizing autoantibody, resulting in low ratio of ADAMTS13 to VWF. The patient was treated intensively, including plasma exchange, and he recovered from the TMA. He developed pulmonary embolism (PE), however, after removal of the central venous catheter. The findings suggested that influenza-associated cytokines enhanced the release of unusually large VWF multimers from vascular endothelial cells and promoted the formation of platelet thrombi and TMA. Subsequent analysis further indicated the presence of familial protein S deficiency, and it seemed likely that the PE was more related to this heterozygous protein S defect.

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Agronomic fortification of rice grains with secondary and micronutrients under differing crop management and soil moisture regimes in the north Indian Plains

Dass

Chandra

Uphoff

et al. 2017

Paddy Water Environ

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Late onset thrombosis in two Japanese patients with compound heterozygote protein S deficiency

Cited by 6 publications

References 9 publications

Compound heterozygous mutations identified in severe type I protein S deficiency impaired the secretion of protein S

Compound heterozygous mutations identified in severe type I protein S deficiency impaired the secretion of protein S

Influenza‐associated thrombotic microangiopathy with unbalanced von Willebrand factor and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 levels in a heterozygous protein S‐deficient boy

Agronomic fortification of rice grains with secondary and micronutrients under differing crop management and soil moisture regimes in the north Indian Plains

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