Homozygosity for R87H missense mutation and for a rare intron 7 DNA variant (7054G→A) in thePROCgenes of three siblings initially classified as heterozygotes for protein C deficiency
作者:
J. Soria,
M. Morell,
I. Nicolau,
X. Estivill,
N. Sala,
期刊:
Blood Coagulation and Fibrinolysis
(OVID Available online 1996)
卷期:
Volume 7,
issue 1
页码: 15-23
ISSN:0957-5235
年代: 1996
出版商: OVID
关键词: PC deficiency;PROC gene mutations;PC anticoagulant activity;mRNA analysis
数据来源: OVID
摘要:
We report the results of protein C gene (PROC) analysis in a Spanish family with hereditary PC deficiency characterized by the presence of three siblings with PC anticoagulant activity levels clearly below 50% of normal and PC antigen and amidolytic activities between 50 and 75% of normal. Their parents are first cousins and have PC levels between 50 and 80% of normal. Sequence analysis of the whole coding sequence of thePROCgene revealed that the three siblings are double homozygotes for a G to A transition at nucleotide 3203 that replaces arginine 87 by histidine (R87H) and for another G to A transition at nucleotide 7054, in intron 7 (7054G → A). Both parents and one sister were found to be double heterozygotes for these two mutations. Screening for the intronic mutation in a control group and RT-PCR cDNA studies from ectopically transcribed mRNA indicated that 7054G→A is most likely a rare but neutral DNA variant. These results and the fact that heterozygosity for the missense R87H mutation has also been found associated with a slightly decreased PC anticoagulant activity in another Spanish family, lead us to conclude that homozygosity for R87H is responsible for the PC deficient phenotype in these three siblings.
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