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

BackgroundSevere 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).ProcedureWe studied the onset of disease and the genotype of 22 PCâ deficient patients with double mutations in PROC based on our cohort (n = 12) and the previous reports (n = 10) in Japan.ResultsTwentyâ 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: 19â 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 lateâ 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.ConclusionsThe genotype of doubleâ PROC mutants might show less diversity than heterozygous mutants in terms of the timing of the onset of thrombophilia (newborn onset or late onset).Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137364/1/pbc26404_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137364/2/pbc26404.pd

2011/12及び2012/13年インフルエンザ流行期に患者より分離されたA/H3N2型ウイルス96株のNA遺伝子配列と薬剤感受性との関連についての検討

Background : Influenza virus has neuraminidase (NA), a surface protein with enzymatic activity that is essential for virus replication. Mutation may affect the effectiveness of NA inhibitors that are used for the treatment of influenza patients. In this study, we determined the NA gene sequences from the clinical isolates of influenza patients to examine the chronological genetic changes and the relation to drug susceptibility. Methods : For 96 A/H3N2 virus isolates the 50% inhibitory concentration (IC_<50>) (48 each from the 2011-12 and 12-13 influenza seasons) was measured. RT-PCR was done with extracted viral RNA, followed by nucleotide sequencing. Results : One putative amino acid mutation, D151N, was found in an NA activity-related cite in five of ninety-six tested isolate. The mutation did not affect the IC_<50> value. The mutations identified at amino acid positions 387 and 400 were statistically correlated with an increased IC_<50> value, although the change was less than ten times, suggesting no significant difference in the clinical effectiveness. A small number of isolates showed mutation in the T and/or B cell epitope region of NA. Conclusion : No mutation that affected the IC_<50> value or effectiveness of NAIs was detected. Antigenic mutations of NA, which influence the selection of epidemic strains, were not determined. Continuous observation will be necessary to further clarify the genetic features of NA