The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene

Hirofumi Inoue, Shin Ichi Terachi, Takeshi Uchiumi, Tetsuji Sato, Michiyo Urata, Masataka Ishimura, Yui Koga, Taeko Hotta, Toshiro Hara, Dongchon Kang, Shouichi Ohga

研究成果: ジャーナルへの寄稿記事

5 引用 (Scopus)

抄録

Background: Severe protein C (PC) deficiency is a rare heritable thrombophilia leading to thromboembolic events during the neonatal period. It remains unclear how individuals with complete PC gene (PROC) defects develop or escape neonatal stroke or purpura fulminans (PF). Procedure: We studied the onset of disease and the genotype of 22 PC-deficient patients with double mutations in PROC based on our cohort (n = 12) and the previous reports (n = 10) in Japan. Results: Twenty-two patients in 20 unrelated families had 4 homozygous and 18 compound heterozygous mutations. Sixteen newborns presented with PF (n = 11, 69%), intracranial thromboembolism and hemorrhage (n = 13, 81%), or both (n = 8, 50%), with most showing a plasma PC activity of <10%. Six others first developed overt thromboembolism when they were over 15 years of age, showing a median PC activity of 31% (range: 19–52%). Fifteen of the 22 patients (68%) had the five major mutations (G423VfsX82, V339M, R211W, M406I, and F181V) or two others (E68K and K193del) that have been reported in Japan. Three of the six late-onset cases, but none of the 16 neonatal cases, had the K193del mutation, which has been reported to be the most common variant of Chinese thrombophilia. A novel mutation of A309V was determined in a family of two patients with late onset. Conclusions: The genotype of double-PROC mutants might show less diversity than heterozygous mutants in terms of the timing of the onset of thrombophilia (newborn onset or late onset).

元の言語英語
記事番号e26404
ジャーナルPediatric Blood and Cancer
64
発行部数7
DOI
出版物ステータス出版済み - 7 2017

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Protein C Deficiency
Protein C
Genotype
Thrombophilia
Mutation
Purpura Fulminans
Genes
Thromboembolism
Japan
Newborn Infant
Intracranial Hemorrhages
Blood Proteins
Stroke

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

これを引用

The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene. / Inoue, Hirofumi; Terachi, Shin Ichi; Uchiumi, Takeshi; Sato, Tetsuji; Urata, Michiyo; Ishimura, Masataka; Koga, Yui; Hotta, Taeko; Hara, Toshiro; Kang, Dongchon; Ohga, Shouichi.

:: Pediatric Blood and Cancer, 巻 64, 番号 7, e26404, 07.2017.

研究成果: ジャーナルへの寄稿記事

Inoue, Hirofumi ; Terachi, Shin Ichi ; Uchiumi, Takeshi ; Sato, Tetsuji ; Urata, Michiyo ; Ishimura, Masataka ; Koga, Yui ; Hotta, Taeko ; Hara, Toshiro ; Kang, Dongchon ; Ohga, Shouichi. / The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene. :: Pediatric Blood and Cancer. 2017 ; 巻 64, 番号 7.
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title = "The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene",
abstract = "Background: Severe protein C (PC) deficiency is a rare heritable thrombophilia leading to thromboembolic events during the neonatal period. It remains unclear how individuals with complete PC gene (PROC) defects develop or escape neonatal stroke or purpura fulminans (PF). Procedure: We studied the onset of disease and the genotype of 22 PC-deficient patients with double mutations in PROC based on our cohort (n = 12) and the previous reports (n = 10) in Japan. Results: Twenty-two patients in 20 unrelated families had 4 homozygous and 18 compound heterozygous mutations. Sixteen newborns presented with PF (n = 11, 69{\%}), intracranial thromboembolism and hemorrhage (n = 13, 81{\%}), or both (n = 8, 50{\%}), with most showing a plasma PC activity of <10{\%}. Six others first developed overt thromboembolism when they were over 15 years of age, showing a median PC activity of 31{\%} (range: 19–52{\%}). Fifteen of the 22 patients (68{\%}) had the five major mutations (G423VfsX82, V339M, R211W, M406I, and F181V) or two others (E68K and K193del) that have been reported in Japan. Three of the six late-onset cases, but none of the 16 neonatal cases, had the K193del mutation, which has been reported to be the most common variant of Chinese thrombophilia. A novel mutation of A309V was determined in a family of two patients with late onset. Conclusions: The genotype of double-PROC mutants might show less diversity than heterozygous mutants in terms of the timing of the onset of thrombophilia (newborn onset or late onset).",
author = "Hirofumi Inoue and Terachi, {Shin Ichi} and Takeshi Uchiumi and Tetsuji Sato and Michiyo Urata and Masataka Ishimura and Yui Koga and Taeko Hotta and Toshiro Hara and Dongchon Kang and Shouichi Ohga",
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T1 - The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene

AU - Inoue, Hirofumi

AU - Terachi, Shin Ichi

AU - Uchiumi, Takeshi

AU - Sato, Tetsuji

AU - Urata, Michiyo

AU - Ishimura, Masataka

AU - Koga, Yui

AU - Hotta, Taeko

AU - Hara, Toshiro

AU - Kang, Dongchon

AU - Ohga, Shouichi

PY - 2017/7

Y1 - 2017/7

N2 - Background: Severe protein C (PC) deficiency is a rare heritable thrombophilia leading to thromboembolic events during the neonatal period. It remains unclear how individuals with complete PC gene (PROC) defects develop or escape neonatal stroke or purpura fulminans (PF). Procedure: We studied the onset of disease and the genotype of 22 PC-deficient patients with double mutations in PROC based on our cohort (n = 12) and the previous reports (n = 10) in Japan. Results: Twenty-two patients in 20 unrelated families had 4 homozygous and 18 compound heterozygous mutations. Sixteen newborns presented with PF (n = 11, 69%), intracranial thromboembolism and hemorrhage (n = 13, 81%), or both (n = 8, 50%), with most showing a plasma PC activity of <10%. Six others first developed overt thromboembolism when they were over 15 years of age, showing a median PC activity of 31% (range: 19–52%). Fifteen of the 22 patients (68%) had the five major mutations (G423VfsX82, V339M, R211W, M406I, and F181V) or two others (E68K and K193del) that have been reported in Japan. Three of the six late-onset cases, but none of the 16 neonatal cases, had the K193del mutation, which has been reported to be the most common variant of Chinese thrombophilia. A novel mutation of A309V was determined in a family of two patients with late onset. Conclusions: The genotype of double-PROC mutants might show less diversity than heterozygous mutants in terms of the timing of the onset of thrombophilia (newborn onset or late onset).

AB - Background: Severe protein C (PC) deficiency is a rare heritable thrombophilia leading to thromboembolic events during the neonatal period. It remains unclear how individuals with complete PC gene (PROC) defects develop or escape neonatal stroke or purpura fulminans (PF). Procedure: We studied the onset of disease and the genotype of 22 PC-deficient patients with double mutations in PROC based on our cohort (n = 12) and the previous reports (n = 10) in Japan. Results: Twenty-two patients in 20 unrelated families had 4 homozygous and 18 compound heterozygous mutations. Sixteen newborns presented with PF (n = 11, 69%), intracranial thromboembolism and hemorrhage (n = 13, 81%), or both (n = 8, 50%), with most showing a plasma PC activity of <10%. Six others first developed overt thromboembolism when they were over 15 years of age, showing a median PC activity of 31% (range: 19–52%). Fifteen of the 22 patients (68%) had the five major mutations (G423VfsX82, V339M, R211W, M406I, and F181V) or two others (E68K and K193del) that have been reported in Japan. Three of the six late-onset cases, but none of the 16 neonatal cases, had the K193del mutation, which has been reported to be the most common variant of Chinese thrombophilia. A novel mutation of A309V was determined in a family of two patients with late onset. Conclusions: The genotype of double-PROC mutants might show less diversity than heterozygous mutants in terms of the timing of the onset of thrombophilia (newborn onset or late onset).

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DO - 10.1002/pbc.26404

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