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The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene
Author(s) -
Inoue Hirofumi,
Terachi Shinichi,
Uchiumi Takeshi,
Sato Tetsuji,
Urata Michiyo,
Ishimura Masataka,
Koga Yui,
Hotta Taeko,
Hara Toshiro,
Kang Dongchon,
Ohga Shouichi
Publication year - 2017
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.26404
Subject(s) - medicine , purpura fulminans , thrombophilia , genotype , protein c , compound heterozygosity , protein c deficiency , pediatrics , mutation , cohort , gastroenterology , gene mutation , genetics , gene , surgery , thrombosis , biology , venous thrombosis
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).