Protein C and XXXX assessment in hospital laboratories: which strategy and what role for DNA sequencing?

@entity1 @entity4889 @entity7131 @entity70587 @entity5448 @entity715
This paper presents a critical assessment of protein C (PC) and @entity4889 ( @entity4889 ) functional and immunological approaches with regard to DNA sequencing in a large hospital recruitment for @entity715 exploration in more than 1700 consecutive @entity1 . After examination of clinical status and PC and @entity4889 phenotype, a genotypic study was implemented for 17 @entity7131 and 28 @entity4889 @entity1 (activity < 70%). Sixty-five percent of the genotyped @entity7131 @entity1 were found to have heterozygous mutations. Among the < 70% values, decreases in PC activity without gene mutation were always slight (mean value 64 +/- 7%) while @entity1 presenting a PC gene mutation had a mean 50 +/- 17% activity (P < 0.05). Among the eight PC mutations found, only one has previously been described. A novel mutation in the promoter region (-1522), located in the @entity5448 site and associated with the @entity70587 heterozygous mutation, was found in a 9-month-old @entity1 with 4% PC activity. Determination of @entity4889 functional activity was considerably improved by contemporaneous measurement of calibration and samples in a single step. Only 50% of the genotyped @entity4889 @entity1 demonstrated heterozygous alterations of the gene. The benefit of sequencing to identify putative causal mutations was only 39% in @entity4889 @entity1 , while it was 90% in @entity1 . Among the nine @entity4889 mutations found, six have not yet been published. In the present paper, we explain our methodological choices and diagnostic strategy.
