Homozygosity for R87H missense mutation and for a rare intron 7 DNA variant (7054G→A) in the PROC genes of three siblings initially classified as heterozygotes for protein C deficiency

J. M. Soria, M. Morell, I. Nicolau, Xavier P. Estivill, N. Sala

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Abstract

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 the PROC gene 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.

Original languageEnglish
Pages (from-to)15-23
Number of pages9
JournalBlood Coagulation and Fibrinolysis
Volume7
Issue number1
Publication statusPublished - 1996
Externally publishedYes

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Keywords

  • mRNA analysis
  • PC anticoagulant activity
  • PC deficiency
  • PROC gene mutations

ASJC Scopus subject areas

  • Hematology

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